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Drugs, biogenic amine targets and the developing brain.

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  • 1. Neuroscience Graduate Program, Vanderbilt University, Nashville, TN 37232-6600, USA.
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    • Frederick AL 1
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Developmental Neuroscience, 17 Apr 2009, 31(1-2):7-22
https://doi.org/10.1159/000207490 PMID: 19372683 PMCID: PMC2786771

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Abstract 

Defects in the development of the brain have a profound impact on mature brain functions and underlying psychopathology. Classical neurotransmitters and neuromodulators, such as dopamine, serotonin, norepinephrine, acetylcholine, glutamate and GABA, have pleiotropic effects during brain development. In other words, these molecules produce multiple diverse effects to serve as regulators of distinct cellular functions at different times in neurodevelopment. These systems are impacted upon by abuse of a variety of illicit drugs, neurotherapeutics and environmental contaminants. In this review, we describe the impact of drugs and chemicals on brain formation and function in animal models and in human populations, highlighting sensitive periods and effects that may not emerge until later in life.

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Dev Neurosci. Author manuscript; available in PMC 2009 Dec 1.
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PMCID: PMC2786771
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PMID: 19372683

Drugs, Biogenic Amine Targets and the Developing Brain

Aliya L. Frederick1 and Gregg D. Stanwood2,3
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Abstract

Defects in the development of the brain have profound impacts on mature brain functions and underlie psychopathology. Classical neurotransmitters and neuromodulators, such as dopamine, serotonin, norepinephrine, acetycholine, glutamate and GABA, have pleiotropic effects during brain development. In other words, these molecules produce multiple, diverse effects to serve as regulators of distinct cellular functions at different times in neurodevelopment. These systems are impacted upon by a variety of illicit drugs of abuse, neurotherapeutics, and environmental contaminants. In this review, we describe the impact of drugs and chemicals on brain formation and function in animal models and in human populations, highlighting sensitive periods and effects that may not emerge until later in life.

Keywords: dopamine, serotonin, norepinephrine, cocaine, amphetamine, prenatal cocaine, postnatal development, 5-HT, developmental neurotoxicity, cognitive development

Many Drugs of Abuse and Therapeutics Target Biogenic Amines

Biogenic amines are a group of neurotransmitters derived by the enzymatic decarboxylation of naturally occurring amino acids. These transmitters include the catecholamines, dopamine and norepinephrine, as well serotonin and acetycholine. Each of these neurotransmitters has characteristic properties of synthesis, packaging, release, targets, degradation and action that allow its characterization at the synapse. Biogenic amines are implicated in a wide range of behaviors, cognitive functions and homeostatic functions in the mature central nervous system (CNS). However, these neuromodulators appear early during embryogenesis, well before the onset of synaptogenesis, suggesting that they also play important roles in brain development. It is therefore not surprising that alterations to these systems, either by pharmacological agents that affect synthesis or binding in the mature system, or developmentally due to toxic insults or genetic modifications, will have important consequences on the brain. In this review we will particularly emphasize the role of the developing dopamine system, but also describe data implicating noradrenergic and serotonergic projections. For discussion of other neurotransmitter systems and drug targets during development, we refer the reader elsewhere (Slotkin 1998; Francis et al. 1999; Olney et al. 2002; Abreu-Villaca et al. 2003; Herlenius and Lagercrantz 2004; Rodier 2004; Holmes et al. 2005).

Dopamine (DA)

DA is widely distributed in the adult CNS and serves a variety of functions in the mature brain, including control of movement. DA is also involved in regulation of the endocrine, limbic and cardiovascular systems. DA abnormalities appear to contribute to many neurological and psychiatric disorders, including schizophrenia, Parkinson's disease, attention-deficit hyperactivity disorder, and drug addiction (Kiyatkin 1995; Goldman-Rakic 1998; Nestler 2001; Girault and Greengard 2004; Arnsten and Li 2005; Biederman and Faraone 2005; Kalivas and Volkow 2005). Many drugs used for therapeutic purposes, such as antipsychotics, act directly on the DA system.

All the catecholamines, characterized by a benzene ring with two hydroxyl groups and attached amine group, are derived from the amino acid tyrosine. DA is synthesized from conversion of L-tyrosine into L-dopa by the rate-limiting enzyme, tyrosine hydroxylase. Subsequent activity of DOPA decarboxylase results in conversion to dopamine. DA receptors are characterized by an extracellular N-terminus region, intracellular C-terminus region and seven membrane spanning regions. The receptors are coupled intracellularly to guanine nucleotide binding proteins that induce intracellular signaling cascades to influence regulation of calcium and potassium channels on the postsynaptic membrane. There are two subfamilies of DA receptors based on their pharmacological profiles and sequence homology: D1-like receptors and D2-like receptors. D1-like receptors, including the D1 and D5 receptor subtypes, catalyze the synthesis of cyclic adenosine monophosphate (cAMP) from the action of adenylate cyclase on adenosine triphosphate. D2-like receptors, including the D2, D3, and D4 receptor subtypes, inhibit cAMP synthesis (Kebabian and Calne 1979; Missale et al. 1998). Transmitter action is terminated by re-uptake into the presynaptic terminal by a high affinity plasma membrane dopamine transporter (DAT) and ezymatically degraded by monoamine oxidase (MAO) or catechol-ο-methyl transferase (COMT).

There are several major dopaminergic pathways. The nigrostriatal tract consists of dopaminergic neurons in the substantia nigra (SN) pars compacta that terminate in the striatum, a major DA -containing area of the brain. The striatum is a component of the extrapyramidal motor system and plays an essential role in the coordination of locomotor activity. Degeneration of the neurons in the nigrostriatal pathway is the primary pathological finding in Parkinson's disease resulting in characteristic motor dysfunction. DA is also believed to be involved with the limbic system, particularly in behaviors associated with motivation, reward (endogenous systems and drug abuse) and reinforcement. The mesolimbic and mesocortical pathways are two midbrain dopaminergic pathways implicated in these behaviors. Both pathways begin in the midbrain ventral tegmental area (VTA) and provide input to the nucleus accumbens and frontal cortex (both medial prefrontal (mPFC) and anterior cingulate (ACC)), respectively (Olson et al. 1972). In monkeys, it has also been observed that a subset of VTA neurons provide innervation to the caudate nucleus of the striatum, thus implicating the striatum in the regulation of emotional behaviors in this species (Lynd-Balta and Haber 1994b; Lynd-Balta and Haber 1994a; Haber et al. 1995).

Tyrosine hydroxylase (TH), the rate-limiting enzyme in DA synthesis and a useful marker for identifying DA neurons, is first apparent at Embryonic day (E)12-13 of an approximate 21 day gestational period in the rat midbrain, and is present by E14 of an approximate 30 day gestational period in the rabbit. DA is also likely to have early biological activity in the primate brain. In the monkey, DA neurons of the SN/VTA are produced between E36 and E43 of a 165 day gestational period (Levitt and Rakic 1982). In humans, midbrain DA neurons appear during the first trimester in the second month of gestation (Olson and Seiger 1972). This input is thus already present in the cortex even while more superficial cortical layers (II-IV) are beginning to form, consistent with a morphogenic role of DA.

Axons of dopaminergic cells reach the cortex a few days after their initial detection in the midbrain, innervating the cortex in a bilaminar pattern with greatest input into layers II and/or III and V and/or VI depending upon the cortical region in the monkey. This stands in contrast with the innervation pattern in rodents in which there is substantial innervation of layer I as well as overlap between thalamic and catecholamine neurons in layer IV (Levitt et al. 1984). Limbic cortical regions, such as the ACC and mPFC receive the densest dopaminergic innervation. The density of tyrosine hydroxylase-positive axons in the cortex increases gradually over development then declines postnatally to reach adult levels during puberty. This protracted postnatal increase in dopamine content occurs over a time period during which a number of developmental milestones occur that may involve transmitter signaling including obtaining competency on working memory tasks (Lambe et al. 2000).

Fluorescent histochemical analysis of DA afferents in the cortex shows regional differences in DA input that correspond well with the heterogeneous distribution of endogenous DA content assayed biochemically in the cortex (Brown et al. 1979; Reader et al. 1989a). In the monkey, in addition to dense prefrontal DA innervation, there is also substantial DA input to premotor and primary motor cortex as well as the anterior regions of the superior and inferior gyri of the temporal lobe. Minimal contributions of DA afferents, however, are found in the parietal and occipital lobes across species (Levitt et al. 1984; Reader et al. 1989a). The mechanisms responsible for the proper guidance of dopaminergic afferents from the midbrain to the cortex and the morphogenic properties of these afferents on cortical neurons are not well-understood, but netrins and ephrins have been implicated (Yue et al. 1999; Flores et al. 2005; Lin and Isacson 2006).

Transcripts for the D1, D2 and D3 receptors can be detected in the striatum and cortex by E14 in the rat and by E12 in the mouse (Jung and Bennett 1996; Araki et al. 2007). D1 and D2 receptors are measurable at these early prenatal time-points and increase in abundance throughout prenatal and early postnatal development to reach adult levels of expression between Postnatal day (P)14 and P21 in rodents (Sales et al. 1989; Rao et al. 1991; Schambra et al. 1994; Caille et al. 1995). In the monkey, DA receptors appear in target regions of DA input by the first quarter of gestation (Lidow et al. 1991; Lidow 1995a) and in humans DA receptor binding sites have been detected by week twelve of gestation (Aubert et al. 1997). Therefore, in all species examined, DA receptors are present very early in prenatal development, consistent with a role for DA in regulating neuronal differentiation and circuit formation. DA receptors have characteristic laminar distribution in the cortex, as observed in the monkey, [3H]-SCH23390 labeled D1 receptors have a bilaminar distribution with highest concentration in the supragranular layers of the cortex (I,II, and IIIa) and deep layers V and VI with relatively few receptors in intermediate strata. [3H]-raclopride labeled D2 receptors, on the other hand, are most concentrated in layer V and exist in lower densities than D1 receptors throughout the cortex (Goldman-Rakic et al. 1990; Lidow et al. 1991). Dense DA innervation into the superficial layers of cortex may be a primate specialization as binding in these layers has not been observed in rodents. The anatomical distribution of cortical DA receptors is heterogeneous throughout various brain regions and corresponds with concentration of DA fiber input and endogenous DA and metabolites.

The majority of work thus presented has been done in the rodent, although comparisons have been made between species with available data on non-human primates and humans when possible and less often with rabbits. The characterization of the DA system in rabbits validates it as a relevant animal model for study (see section on prenatal cocaine, below). Pharmacological agents used to characterize D1 receptors in the rat, non-human primate and humans have similarly been used in rabbits to characterize high-affinity receptors in the cortex and striatum with similar pharmacological profiles as described in the aforementioned species (Reader et al. 1989b). Similarly, D2 receptors have been characterized in the rabbit striatum and cortex (Dewar et al. 1989). In the rabbit CNS, high levels of DA content are present within the ACC while other cortical areas such as the somatosensory cortex and visual cortex have low levels of endogenous content. Highest concentrations of dopamine, as similarly observed in other species studied, are in the neostriatum with no differences between lateral and medial caudate or putamen in the rabbit. Receptor densities are heterogeneous between brain regions with highest concentration of D1 and D2 receptors in the striatum. In the striatum, D2 receptors exist in a lateral to medial gradient in the caudate, findings consistent with observations in the rat. In the cortex, D1 receptor density is significantly lower than in the striatum, but corresponds with areas of DA innervation. D2 receptor density is also heterogenous and less that D1 receptor density in the cortex (Dewar et al. 1989; Dewar and Reader 1989; Reader et al. 1989b).

In vitro studies have supported a role for DA as both a promoter and an inhibitor of neurite growth (Todd 1992; Reinoso et al. 1996; Song et al. 2002; Stanwood and Levitt 2007). The actions of DA on outgrowth are modified by the complement of receptors that are activated, and as a function of the neuronal cell type being modulated. For example, in cortical neurons, selective D1 receptor activation decreases neurite outgrowth in a dose-dependent manner whereas D2 receptor activation increases outgrowth. In striatal neurons, however, these effects are reversed, with D1 receptor activation serving to promote neuronal differentiation and process outgrowth. DA signaling also appears to be involved in prenatal neurogenesis itself within the neuroepithelial precursors of the striatum and cerebral cortex, via influences on cell cycle length (Ohtani et al. 2003; Zhang et al. 2005). The phenotypic differentiation and migration of inhibitory GABAergic interneurons may also be modulated by dopaminergic stimulation (Crandall et al. 2007). Studies from our laboratory and others investigating the effects of prenatal cocaine exposure suggest that modification of DA D1 receptor signaling during a sensitive period of prenatal development induces permanent effects on circuit formation and function (see below). Recent data also suggests that transient overexpression of the D2 receptor in the developing striatum can cause life-long changes in the activity of D1 receptor systems in the prefrontal cortex (Kellendonk et al. 2006). Finally, DA-dependent processes also alter postnatal development of brain circuits, especially during the periods of synaptic maturation and refinement.

Norepinephrine (NE) or Noradrenaline

NE is synthesized and released by adrenergic axon terminals in both the CNS and the sympathetic division of the autonomic nervous system. In the CNS, the cell bodies of NE neurons are concentrated in the brainstem, particularly in the locus coeruleus of the dorsal pons where they are involved in diffuse projections to the neocortex (Segal et al. 1973; Levitt and Moore 1978; Lindvall et al. 1978; Levitt et al. 1984). NE is involved in mediating attention, anxiety, arousal, feeding behaviors and learning and memory.

NE neurons are born at a relatively early time in the CNS of monkeys during the first quarter of gestation, approximately E30 for neurons in the medial locus coeruleus and E32/E33 for those situated more laterally. In rats, fluorescently labeled neurons are observed in the nucleus early in gestation, at approximately E13 (Olson and Seiger 1972; Lauder and Bloom 1974b). The majority of NE axon terminals ascend to the forebrain in the dorsal tegmental bundle, dessucating almost immediately or more rostrally to join the ascending medial forebrain bundle. Flourescence histochemistry suggests that developing axons enter the neocortex across multiple cortical layers, however as the cortex matures, NE afferent input is most concentrated in a bilaminar pattern, predominantly in layers II and/or III (superficial) and V and/or VI (deep). There is heterogenerity in density of NE input between cortical regions with somatosensory cortex receiving the densest NE innervation. NE fibers are also found intermingled with DA neurons in areas of the prefrontal cortex as well anterior parts of the superior and inferior temporal gyri. NE innervation is sparsest in posterior parietal areas and occipital lobes including visual cortex (Levitt et al. 1984; Reader et al. 1989a). These synapses mature during early postnatal life and the adult pattern of innervation is obtained by the end of the first postnatal week in rodents (Lauder and Bloom 1975; Levitt and Moore 1979). In primates, there is a considerably longer maturation process postnally as the first postnatal week in rodents in equivalent to the third trimester in primates.

NE synthesis requires DA as a precursor substrate. DA is trafficked by vesicular transport into adrenergic terminals where it is converted to NE by the enzymatic activity of dopamine β-hydroxylase (Segal et al. 1973). Receptors sensitive to NE are divided into two classes, α– and β–adrenergic receptors based upon the physiological response to catecholamines. The classes are further divided into subtypes, of which there exists α1, α2, β1, and β2 based on pharmacological profiles. In rodents, α1 and α2 adrenoreceptor expression can be detected one day after birth by specific radioligand binding. Receptor binding increases with age reaching a peak between P18-P21 before declining to reach adult levels after the fourth postnatal week (Morris et al. 1980). A similar trend in ontogeny is apparent with β-adrenergic receptors, with these receptors not being detected before P7 (Harden et al. 1977; Pittman et al. 1980).

[3H]-clonidine labeled α2 receptors in the monkey are predominately found in the superficial layers of the cortex with a descending concentration gradient from layer I to VI. Similarly, the density of [3H]-prazosin labeled α1 receptors decreases from layers I to IV, however, there is a slight increase in receptor concentration in the deeper cortical layers. β1 and β2 receptors are most concentrated in the intermediate layers of the cortex (Goldman-Rakic et al. 1990). Species differences exist between the primate and rodents in stratification of receptor density. In the rat, the highest concentration of α1 receptors are found in layers III and IV and β receptors are homogenously distributed. Both types of receptors alter the postsynaptic membrane potential by acting upon potassium and calcium channels. Like DA, NE is terminated by re-uptake into the presynaptic terminal by a high affinity transporter (NET), where it is enzymatically degraded or inactivated by monoamine oxidase (MAO).

Serotonin (5-hydroxytryptamine; 5-HT)

5-HT is a well know modulator of a variety of cognitive and behavioral functions including sleep, sexual urge, anxiety, appetite, temperature regulation, learning and memory, and mood. As such, 5-HT imbalances are implicated in a variety of disorders such as depression, anxiety disorders and aggression (Olivier et al. 1995; Lucki 1998; Gingrich and Hen 2001). 5-HT also exerts influence during specific critical periods during early development. Accumulated evidence indicates that 5-HT plays a role in many developmental processes including neurogenesis, neuronal migration and differentiation, synaptogenesis, and craniofacial, cardiac and limb development prior to assuming is role as a neurotransmitter in the mature brain (Whitaker-Azmitia 2001; Gaspar et al. 2003; Persico et al. 2006). 5-HT also plays crucial roles in thalamocortical patterning (Lebrand et al. 1996; Rebsam et al. 2002; Bonnin et al. 2007).

Serotonergic neurons are among the earliest neurons to be generated during development of the brain. In the monkey, serotonergic neurogenesis in the brainstem raphe nuclei is evident by the end of the first month of gestation in two distinct phases. Neurons in rostral raphe nuclei are generated between E28-E35 with a peak genesis around E30. Caudal raphe nuclei are generated somewhat later with peak neurogenesis between E38-E40 (Levitt and Rakic 1982). In rodents, 5-HT neurons are evident in the midbrain by E12 (Lauder and Bloom 1974a), and by the fifth week of gestation in humans (Olson and Seiger 1972; Sundstrom et al. 1993; Lambe et al. 2000). One day after their generation, serotonergic neurons in the raphe can synthesize and release 5-HT from their growing axonal processes (Lidov and Molliver 1982; Lambe et al. 2000). Serotonergic terminals are found broadly throughout the forebrain including the thalamus and cortex. In the cortex, serotonergic input is greatest in visual and somatosensory cortical areas and less in prefrontal and temporal cortical regions. 5-HT levels increase prenatally through the early postnatal years before declining to reach adult levels (Whitaker-Azmitia 2001).

Numerous 5-HT receptors exist and are grouped into seven different families based on molecular cloning. Additional receptor motifs are created through the acts of mRNA splicing and editing events. Each receptor subtype possesses distinct cellular and/or regional distributions, pharmacological profiles and signal transduction systems. Most 5-HT receptors are heterotrimeric G-protein coupled receptors that activate calcium and potassium channels through intracellular signaling cascades. 5-HT4, 5-HT6, and 5-HT7 receptors couple to the stimulatory Gsα protein to increase activity of adenylate cyclase. 5-HT3 receptors, however, are ligand-gated ion channels (Hartig 1994; Jackson and Yakel 1995).

5-HT receptors are also expressed early in prenatal development (Hellendall et al. 1993; Bonnin et al. 2006). For example, 5-HT2 receptor immunoreactivity is initially apparent in the cortex between E19 and P0 in rodents. After birth there is a rapid increase in expression levels in layers II-VI followed by gradual decline to adult levels beginning around the second postnatal week (Morilak and Ciaranello 1993). In the adult, 5-HT2 receptors are concentrated in the intermediate strata III and IV of the cortex. Receptor localization is consistent between rodents, monkey and humans (Goldman-Rakic et al. 1990; Morilak and Ciaranello 1993). Similarly, the same developmental trend is observed for expression of 5-HT1 receptors. At birth, the percentage of receptors expressed varies among brain regions with densities ranging from 5-50% of adult levels. There is then a transient increase in expression levels followed by a decrease to adult levels during the first postnatal month (Pranzatelli 1993). In the adult monkey, 5-HT1 receptors are found in highest concentrations in the superficial layers of the cortex (Goldman-Rakic et al. 1990). 5-HT1 receptor localization is consistent between monkey and human, while in the rat, receptor density is greatest in layer V (Hoyer et al. 1986).

The synaptic effects of 5-HT are terminated by re-uptake of the neurotransmitter into the presynaptic nerve terminals through a high-affinity 5-HT transporter (SERT). After re-uptake, 5-HT is subsequently degraded by the enzymatic catabolic activity of MAO. A number of neurotherapeutic drugs used in the treatment of depression and anxiety disorders act by inhibiting re-uptake of the transmitter by SERT (Blakely et al. 1994; Jayanthi and Ramamoorthy 2005; White et al. 2005).

Developmental Cocaine Exposure Alters Neurobehavioral Development

The primary pharmacological sites of action of cocaine and other psychostimulants in the brain are the high-affinity transporters for DA, 5-HT and NE. Cocaine binds to these transporter proteins and blocks the re-uptake of the neurotransmitters, thus prolonging their time in the extracellular space. This permits the monoamine to bind to its receptor proteins for more sustained periods, resulting in excessive activation of these receptors, particularly those located extrasynaptically. Cocaine, a drug of abuse in adolescents and adults, produces a host of neuroadaptations in the brain of the user which are associated with addiction (Hyman and Malenka 2001), and can potently modulate monoaminergic systems during prenatal development, if the drug is used during pregnancy (Malanga and Kosofsky 2003; Stanwood and Levitt 2004).

Clinical reports on the impact of prenatal cocaine exposure have been diverse, as some suggest gross physical malformations, others observe specific deficits in cognitive and emotional development, and yet others indicate no detectable effects. The variable outcomes are at least in part the result of important covariates such as the timing and amount of cocaine use during pregnancy, polydrug use, and the quality of pre- and postnatal care (Karmel and Gardner 1996; Richardson et al. 1996; Gingras and O'Donnell 1998; Dow-Edwards et al. 1999; Mayes et al. 2003; Singer et al. 2004). In particular, prenatal cocaine exposure can have long-lasting negative effects on cognitive and attention systems. For example, prenatal cocaine exposure predicts poorer perceptual reasoning IQ compared to non-exposed counterparts (Singer et al. 2008), impairments in procedural learning (Mayes et al. 2007), increased behavioral problems in school (Bada et al. 2007), and increased risk for oppositional defiant disorder and attention deficit hyperactivity disorder (Linares et al. 2006).

Different animal models, designed to mimic human drug use during gestation, confirm that prenatal cocaine exposure results in specific and long-lasting behavioral, cellular, and molecular changes (Mayes 2002; Lidow 2003; Harvey 2004; Stanwood and Levitt 2004). However, the extent and nature of the cellular alterations vary across model systems. Deficits range from alterations in basic processes of neocortical development that result in altered cell production, migration, and genetic regulation (Gressens et al. 1992; Lidow 1995b; Lidow and Song 2001; Crandall et al. 2004; Ren et al. 2004; Guerriero et al. 2005; Lee et al. 2008; Novikova et al. 2008), to more subtle changes in cellular morphology, and molecular signaling cascades within DA-rich regions of the cerebral cortex (Jones et al. 1996; Jones et al. 2000; Stanwood et al. 2001a; Stanwood and Levitt 2003; Stanwood and Levitt 2007). In contrast to the cellular effects, consistent behavioral changes including deficits in attention tasks, emotional reactivity, and the reinforcing properties of drugs of abuse that correspond with the human clinical literature are observed in a variety of animal models of prenatal cocaine exposure (Morrow et al. 2002; Rocha et al. 2002; Gabriel et al. 2003; Stanwood and Levitt 2003; Thompson et al. 2005b; Malanga et al. 2008).

One unique animal model of prenatal cocaine exposure to study the mechanisms underlying the complex, long-term adaptive changes and the functional outcomes of in utero cocaine exposure utilizes a low-dose regimen of intravenous prenatal cocaine exposure in the rabbit, which was initially selected for ease of intravenous administration. Furthermore, the pharmacokinetic profile of intravenous cocaine in the rabbit (Parlaman et al. 2007) closely models what is seen when human users abuse cocaine (Evans et al. 1996; Jenkins et al. 2002). A number of studies have established that the prenatal dosing is not generally teratogenic, nor does it impact basic developmental parameters such as kit mortality, litter size, sex or growth rates (Wang et al. 1995b; Jones et al. 1996; Wang et al. 1996; Murphy et al. 1997). However, through control of length of drug exposure, age at drug exposure, and dosing, we have delineated a critical window of time (E16-25) during which exposure to cocaine affects behavior, morphology, and cellular composition (Stanwood et al. 2001a; Stanwood et al. 2001b; Stanwood and Levitt 2003; Thompson et al. 2005b). This window of time corresponds to the emergence of pre- and postsynaptic components of the DA system in the cerebral cortex (Stanwood et al. 2001a).

Neuroanatomical and molecular analyses in this model have delineated a number of highly specific changes in DA-rich cortical areas, including changes in GABA content, calcium binding protein expression, and morphological changes in pyramidal cells (Murphy et al. 1997; Jones et al. 2000; Stanwood and Levitt 2001; Stanwood et al. 2001b; Stanwood et al. 2006; Stanwood and Levitt 2007). The specific neuronal morphology alterations include a 40-50% increase in pyramidal neuron apical dendrite length within DA rich cortical areas (Jones et al. 2000), which are involved in cognition and executive functioning tasks, including attention (Goldman-Rakic 1996; Collette and Van der Linden 2002; Elliott 2003; Elston 2003; Clark et al. 2004).

Consistent with the regional selectivity in the anatomical findings, extensive behavioral characterization of rabbits following in utero exposure to cocaine suggest that the behaviors disrupted appear to be limited to those mediated via select DA-rich cortical and sub-cortical regions (Romano and Harvey 1996; Simansky et al. 1998; Gabriel et al. 2003; Stanwood and Levitt 2003; Thompson et al. 2005b). For example, these animals exhibit decreases in spontaneous alternation as measured by the Y-maze following prenatal cocaine exposure (Thompson et al. 2005b). This decrease in attention is not accompanied by changes in open field behavior or two-object recognition. Additionally, offspring exposed to prenatal cocaine show a decreased number of head-bobs, a measure of stereotypy, following a single injection of amphetamine and display a blunted preference for cocaine in a conditioned place preference paradigm (Stanwood and Levitt 2003; Thompson et al. 2005a).

Molecular analyses have determined that the DA D1 receptor exhibits permanent reduced coupling to its cognate G-protein, Gsα, following prenatal cocaine exposure (Wang et al. 1995a; Friedman et al. 1996; Jones et al. 2000). This reduction in coupling is a result of DA D1 receptor remaining internalized and not trafficking properly to the cell membrane where it would then interact with Gsα (Stanwood and Levitt 2007). Adult rabbits exposed to cocaine prenatally also exhibit greatly reduced psychostimulant-induced stereotypies, consistent with diminished D1 receptor signaling (Simansky and Kachelries 1996; Stanwood and Levitt 2003). It is important to emphasize that other Gsα-coupled receptor signaling is not altered, nor is D2 coupling altered in the DA-rich brain regions (Wang et al. 1995a; Friedman et al. 1996). This selective reduced coupling of the D1 receptor has been implicated in the cellular, morphological, and behavioral changes observed following prenatal cocaine exposure in our model. Additional evidence to support a role for altered D1 receptor signaling at the cellular level comes from our recent study of the D1 receptor knockout mouse, which exhibits similar cellular and morphological changes to the prenatal cocaine exposed rabbits (Stanwood et al. 2005).

Effects of Developmental Amphetamine/Methamphetamine Exposure

Although amphetamine and methamphetamine use and abuse has been present for decades, there has been comparatively (to cocaine) little clinical and basic research on its effects on brain development. Reports have only recently emerged from a large, prospective study (Smith et al. 2006; Smith et al. 2008). Early clinical reports emphasized increases in premature delivery, placental abruption, cardiac defects, and fetal distress (reviewed in (Plessinger 1998; Smith et al. 2006)). In utero methamphetamine-exposed children are at high risk for growth impairment (Smith et al. 2003) and are 3.5-fold more likely to be smaller than average for gestational age (Smith et al. 2006), perhaps not surprising given the anorectic effects of the drug.

Even fewer studies have examined neurobehavioral outcomes specifically. In neonates, methamphetamine exposure is associated with lower arousal, more lethargy and increased physiological stress (Smith et al. 2008). In a small retrospective study, significant deficits in visuomotor integration, attention, and memory have been observed and linked to smaller volumes of the putamen, globus pallidus and hippocampus (Chang et al. 2004). Imaging studies also point to alterations in striatal energy metabolism in children exposed gestationally (Smith et al. 2001; Chang et al. 2007). It will clearly be important to continue to follow these children for impairments of this nature as they develop and enter schools.

Animal models utilizing a wide variety of species, doses, and timing of exposure have been used to investigate the consequences of prenatal exposure on development. At high doses, methamphetamine induces prominent teratogenic effects on the neonate (Nora et al. 1965; Kasirsky 1971). A very good animal model of third trimester exposure has been developed by Vorhees and colleagues, who inject neonatal rat pups during the ages spanning P11-P21 with multiple, spaced injections. This exposure paradigm produces selective effects on spatial learning and memory (Vorhees et al. 2000; Williams et al. 2003; Vorhees et al. 2007), and both transient and permanent effects in stress hormones and brain biogenic amines (Williams et al. 2005; Schaefer et al. 2008). Interestingly, neonatal methamphetamine exposure does not alter striatal DA levels (Schaefer et al. 2008), very unlike its effect in adult animals, where it produces long lasting decreases in DA (Cappon et al. 2000).

Other groups have reported changes in the structure and myelination of the optic nerve (Melo et al. 2006; Melo et al. 2008), altered seizure susceptibility (Slamberova et al. 2008), and reduced spontaneous motor activity (Cho et al. 1991; Weissman and Caldecott-Hazard 1993) following prenatal methamphetamine exposure. Long-lasting changes in the function of the NE (Nasif et al. 1999) and 5-HT (Tavares et al. 1996) systems have also been described following in utero amphetamine exposure.

Effects of Developmental MDMA Exposure

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a derivative of methamphetamine acting primarily on the 5-HT system to increase 5-HT release. In adults, MDMA produces enhanced mood, euphoria, heightened sensory awareness, and sympathetic arousal including tachycardia and hyperthermia (Lyles and Cadet 2003). At high doses, MDMA is capable of neurotoxicity. MDMA also passes through the placental barrier to enter into the fetal circulation (Campbell et al. 2006), suggesting that MDMA use during pregnancy is capable of inducing effects in the offspring. 5-HT has well-documented effects on early development of the brain and other organs (Cases et al. 1996; Bonnin et al. 2007; Cote et al. 2007), raising concerns about deleterious effects of MDMA use during pregnancy.

In fact, a preliminary study of prenatal MDMA-exposed children demonstrated increased risks of cardiovascular and musculoskeletal abnormalities following exposure during the first trimester (McElhatton et al. 1999). Prenatal exposure in animal models and culture systems also suggest deleterious effects of MDMA on the development of dopaminergic and serotonergic neurons (Won et al. 2002; Koprich et al. 2003; Galineau et al. 2005) and increases in locomotor activity in adolescent offspring (Koprich et al. 2003). Third trimester equivalent exposure in rats also leads to learning difficulties (Broening et al. 2001; Williams et al. 2003); similar to the effects of the 5-HT releaser d-fenfluramine (Morford et al. 2002). These effects may be due to increased sensitivity of 5-HT1A receptors (Crawford et al. 2006). These effects were recently reviewed in exquisite detail (Piper 2007; Skelton et al. 2008).

Potential Developmental Impact of Therapeutic Medications

Biogenic amine systems are also targeted by psychoactive medications, including antidepressant and antipsychotic drugs. To test for a possible developmental role of the 5-HT system in establishing anxiety circuitry, Hen and colleagues generated a conditional knockout mouse that allowed for temporally-restricted rescue of postsynaptic 5-HT1A receptors in the cerebral cortex and hippocampus (Gross et al. 2002). Using this strategy, they demonstrated that initiating expression of the receptor after P21 resulted in increased anxiety levels identical to constitutive 5-HT1A receptor knockout animals. Conversely, earlier expression of the 5-HT1A receptor, during the first three postnatal weeks, produced mice with anxiety levels that were indistinguishable from wild-type animals, even if the receptor was turned off in adulthood. Administration of the selective 5-HT reuptake inhibitor (SSRI) fluoxetine from P4-P21 also leads to permanent changes in anxiety behavior (Ansorge et al. 2004). These findings indicate that normal 5-HT activity during early postnatal development in the rodent is crucial to the establishment of normal anxiety-modulating circuits in the brain, and that both genetic and environmental factors are capable of influencing these circuits.

Consistent with the rodent models, data from human studies suggest that baseline anxiety levels are influenced early in life. By two years of age, most children have established cohesive patterns of response to novel environments, as measured by behavioral inhibition. These measures appear to be stable over many years (Hirshfeld et al. 1992; Rosenbaum et al. 1993; Schwartz et al. 1999) (although see also (Degnan and Fox 2007)), and can predict one's future risk of anxiety disorders (Kagan and Snidman 1999; Kagan et al. 2007). Not surprisingly, polymorphisms in 5-HT system-related genes have all been associated with anxiety- and depression-related symptoms (Albert and Lemonde 2004; Kim et al. 2006; Walderhaug et al. 2007; Dannlowski et al. 2008; Murphy and Lesch 2008). Many prominent psycho-therapeutics target the 5-HT system and are utilized for depression and anxiety among pregnant and nursing mothers. Published literature to date suggests only modest alterations in neonatal outcome (Pearson et al. 2007; Andrade et al. 2008; Maschi et al. 2008; Oberlander et al. 2008), but further study of the neurobehavioral consequences of antidepressant exposure on the developing fetus and infant are clearly needed. Possible long-lasting changes in drug-seeking behavior following maternal SSRI exposure have also been recently suggested (Forcelli and Heinrichs 2008).

Antipsychotic drugs are another group of therapeutics needed by some pregnant women and young people suffering from schizophrenia and other psychotic illnesses. Again, however, these drugs have potent effects on the development of aminergic systems, especially on DA receptors (Rosengarten and Friedhoff 1979; Moran-Gates et al. 2006). These drugs can also produce long-lasting changes in neurochemistry, brain architecture, and behavior (Scalzo and Spear 1985; Scalzo et al. 1993; Singh and Singh 2001; Rosengarten and Quartermain 2002; Singh and Singh 2002; Wang et al. 2006).

Another intriguing and unexpected example has come from developmental studies of terbutaline, a β-adrenoceptor agonist used to arrest preterm labor. However, the drug also crosses the placenta and blood-brain barrier. Early postnatal exposure to terbutaline in rats, a period corresponding to the third trimester in humans, produces long-lasting alterations in NE innervation and receptor expression in multiple brain regions (Slotkin et al. 1990; Slotkin et al. 2001; Rhodes et al. 2004; Aldridge et al. 2005; Slotkin and Seidler 2007a), as well as increasing the toxic consequences of subsequent pesticide exposure (see below) (Meyer et al. 2005). Increased microglial activation, behavioral abnormalities, and alterations in 5-HT systems have also been reported (Aldridge et al. 2005; Zerrate et al. 2007). In humans, it has been suggested that terbutaline treatment during pregnancy may lead to an increased incidence of autism spectrum disorder in offspring (Connors et al. 2005); similarly gain-of-function polymorphisms in the β2-adrenergic receptor which produce receptors that are resilient to desensitization have been associated with autism (Connors et al. 2005; Cheslack-Postava et al. 2007).

Environmental Agents / Toxins

Thousands of new chemicals are produced each year, about 25% of them may be neurotoxic, but only about 10% of them will ever be tested for such activity (Connors et al. 2008). Long-lasting neurodevelopmental effects on biogenic amine systems and their targets have been described for some of these chemicals and environmental contaminants, including lead (Szczerbak et al. 2007; Nowak et al. 2008), polychlorinated biphenyls (PCBs) (Bushnell et al. 2002; Kuchiiwa et al. 2002), polybrominated diphenyl ethers (Dingemans et al. 2007; Llansola et al. 2007; Alm et al. 2008; Gee and Moser 2008), pyethroids (Nasuti et al. 2007), organic solvents (Hougaard et al. 1999; Gospe and Zhou 2000; Bowen and Hannigan 2006), and synthetic estrogens such as bisphenol-A (Suzuki et al. 2003; Laviola et al. 2005; Miyagawa et al. 2007). These “nondrug” environmental factors can interact with developmental drug exposures and/or genetic factors to produce complex effects on brain formation and function, often at concentration levels that appear to be harmless for adults. For example, perinatal exposure to bisphenol-A can produce long-lasting potentiation of D1 DA receptor function, supersensitivity to methamphetamine, and decreases in the expression of genes crucial for DA neuron development and survival such as sonic hedgehog and glial-derived neurotrophic factor (Suzuki et al. 2003; Suzuki et al. 2005; Miyagawa et al. 2007). Even artificial food colors and preservatives such as sodium benzoate appears to contribute to hyperactivity in children (McCann et al. 2007). It is well beyond the scope of this review to describe all of these compounds in detail (see (Costa et al. 2004; Rodier 2004; Slotkin 2004; Bowen and Hannigan 2006; Johansson et al. 2007; Moser 2007) for more detailed reviews), but we will very briefly discuss two classes of compounds with likely effects on the development of brain biogenic amines and their targets.

Organophosphate pesticides inhibit cholinesterases, and produce cholinergic overstimulation. In addition, developmental exposure to the compounds, such as chlorpyrifos, produces effects on serotonergic synaptic function (Slotkin and Seidler 2007b; Moreno et al. 2008; Roegge et al. 2008). Most exposure occurs through dietary intake (Lu et al. 2008). Importantly, many of these effects on 5-HT and 5-HT-mediated behaviors, such as the development of emotional systems, occur at doses below the threshold for cholinesterase inhibition (Levin et al. 2002; Slotkin et al. 2006; Roegge et al. 2008). Pre and perinatal exposure also produces long-lasting changes in components of brain DA systems, and even increases cell loss at later developmental times following exposure to dopaminergic neurotoxins used to model Parkinson's disease (Richardson et al. 2006). Recent studies identifying functional polymorphisms affecting chlorpyrifos metabolism (Berkowitz et al. 2004) and documenting decreases in cognitive development in children exposed to chlorpyrifos during gestation suggests that this is a very significant human health problem (Rauh et al. 2006; Engel et al. 2007).

Lastly, we describe data regarding manganese, a common naturally occurring heavy metal and essential nutrient. Manganese is crucial for maintaining the proper function and regulation of many biological processes, but is also used in numerous industries including welding, mining, and formulating gasoline additives. Manganese is readily transported into the brain, either as a free ion species or as a nonspecific protein-bound species (Aschner and Gannon 1994). Chronic manganese overexposure results in the onset of a very specific neurological phenotype, known as manganism, which presents with motor symptoms resembling those of Parkinson's disease (Lee 2000; Normandin et al. 2002; Guilarte et al. 2006; Aschner et al. 2007). Similar symptoms have also been described in adults and children receiving prolonged total parenteral nutrition (Kafritsa et al. 1998; Nagatomo et al. 1999; Hsieh et al. 2007), which contains high amounts of manganese (Erikson et al. 2007).

Emerging data from both animal and human studies suggest potent effect of developmental manganese exposure on brain development (Erikson et al. 2007; Ljung and Vahter 2007). For example, manganese exposure during pregnancy and/or early postnatal life produces alterations in locomotor activity, brain monoamine levels, oxidative stress, and brain morphology (Pappas et al. 1997; Tran et al. 2002; Erikson et al. 2006; Reichel et al. 2006). In children, preliminary studies have associated elevated manganese content in drinking water with decreased cognitive and attentional functions (Wasserman et al. 2006; Bouchard et al. 2007). Increased prenatal manganese exposure has also been linked to childhood behavioral disinhibition (Ericson et al. 2007). Moreover, iron deficiency can enhance brain manganese accumulation, even in the absence of excess manganese in the environment, and produce long-lasting changes in metal concentrations and transporters in the brain (Garcia et al. 2007). These data warrant a re-assesment of guideline values for acceptable manganese levels and much more detailed investigations into the risks of environmental manganese exposure.

Conclusions

The mammalian brain develops over a protracted period of time. Neurodevelopment is affected by both genetic and environmental influences, within the context of evolving time. Environmental influences can have effects on brain architecture both prenatally, within the mother's womb, and by the physical and chemical environment experienced after birth. Compounds which affect the construction of brain circuits include legal and illicit psychoactive drugs, used either medicinally or recreationally, as well as environmental toxicants and natural contaminants. Biogenic amine systems may be particularly sensitive to such modulation. Resulting disruptions in brain development sometimes do not emerge until later in life, and may be produced at dose levels that are relatively harmless for adults. This makes the study of these long-term impacts very challenging, but also very crucial. Scientists must continue to inform the public and policy makers of these complex and important issues.

Acknowledgements

Support is received from NICHD core grant P30-HD15052 (GDS), the Vanderbilt Kennedy Center (GDS), and the Vanderbilt Medical Scientist Training Program (ALF). We thank Drs. Pat Levitt and Barbara Thompson for helpful discussions and productive collaborations on the prenatal cocaine model.

References

  • Abreu-Villaca Y, Seidler FJ, Tate CA, Slotkin TA. Nicotine is a neurotoxin in the adolescent brain: critical periods, patterns of exposure, regional selectivity, and dose thresholds for macromolecular alterations. Brain Res. 2003;979:114–128. [Abstract] [Google Scholar]
  • Albert PR, Lemonde S. 5-HT1A receptors, gene repression, and depression: guilt by association. Neuroscientist. 2004;10:575–593. [Abstract] [Google Scholar]
  • Aldridge JE, Meyer A, Seidler FJ, Slotkin TA. Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions. Toxicol Appl Pharmacol. 2005;203:132–144. [Abstract] [Google Scholar]
  • Alm H, Kultima K, Scholz B, Nilsson A, Andren PE, Fex-Svenningsen A, Dencker L, Stigson M. Exposure to brominated flame retardant PBDE-99 affects cytoskeletal protein expression in the neonatal mouse cerebral cortex. Neurotoxicology. 2008;29:628–637. [Abstract] [Google Scholar]
  • Andrade SE, Raebel MA, Brown J, Lane K, Livingston J, Boudreau D, Rolnick SJ, Roblin D, Smith DH, Willy ME, Staffa JA, Platt R. Use of antidepressant medications during pregnancy: a multisite study. Am J Obstet Gynecol. 2008;198:194 e191–195. [Abstract] [Google Scholar]
  • Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA. Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science. 2004;306:879–881. [Abstract] [Google Scholar]
  • Araki KY, Sims JR, Bhide PG. Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development. Brain Res. 2007;1156:31–45. [Europe PMC free article] [Abstract] [Google Scholar]
  • Arnsten AF, Li BM. Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry. 2005;57:1377–1384. [Abstract] [Google Scholar]
  • Aschner M, Gannon M. Manganese (Mn) transport across the rat blood-brain barrier: saturable and transferrin-dependent transport mechanisms. Brain Res Bull. 1994;33:345–349. [Abstract] [Google Scholar]
  • Aschner M, Guilarte TR, Schneider JS, Zheng W. Manganese: recent advances in understanding its transport and neurotoxicity. Toxicol Appl Pharmacol. 2007;221:131–147. [Europe PMC free article] [Abstract] [Google Scholar]
  • Aubert I, Brana C, Pellevoisin C, Giros B, Caille I, Carles D, Vital C, Bloch B. Molecular anatomy of the development of the human substantia nigra. J Comp Neurol. 1997;379:72–87. [Abstract] [Google Scholar]
  • Bada HS, Das A, Bauer CR, Shankaran S, Lester B, LaGasse L, Hammond J, Wright LL, Higgins R. Impact of prenatal cocaine exposure on child behavior problems through school age. Pediatrics. 2007;119:e348–359. [Abstract] [Google Scholar]
  • Berkowitz GS, Wetmur JG, Birman-Deych E, Obel J, Lapinski RH, Godbold JH, Holzman IR, Wolff MS. In utero pesticide exposure, maternal paraoxonase activity, and head circumference. Environ Health Perspect. 2004;112:388–391. [Europe PMC free article] [Abstract] [Google Scholar]
  • Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet. 2005;366:237–248. [Abstract] [Google Scholar]
  • Blakely RD, De Felice LJ, Hartzell HC. Molecular physiology of norepinephrine and serotonin transporters. J Exp Biol. 1994;196:263–281. [Abstract] [Google Scholar]
  • Bonnin A, Peng W, Hewlitt W, Levitt P. Expression mapping of 5-HT1 serotonin receptor subtypes during fetal and early postnatal mouse forebrain development. Neuroscience. 2006 in press. [Abstract] [Google Scholar]
  • Bonnin A, Torii M, Wang L, Rakic P, Levitt P. Serotonin modulates the response of embryonic thalamocortical axons to netrin-1. Nat Neurosci. 2007;10:588–597. [Abstract] [Google Scholar]
  • Bouchard M, Laforest F, Vandelac L, Bellinger D, Mergler D. Hair manganese and hyperactive behaviors: pilot study of school-age children exposed through tap water. Environ Health Perspect. 2007;115:122–127. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bowen SE, Hannigan JH. Developmental toxicity of prenatal exposure to toluene. Aaps J. 2006;8:E419–424. [Europe PMC free article] [Abstract] [Google Scholar]
  • Broening HW, Morford LL, Inman-Wood SL, Fukumura M, Vorhees CV. 3,4-methylenedioxymethamphetamine (ecstasy)-induced learning and memory impairments depend on the age of exposure during early development. J Neurosci. 2001;21:3228–3235. [Abstract] [Google Scholar]
  • Brown RM, Crane AM, Goldman PS. Regional distribution of monoamines in the cerebral cortex and subcortical structures of the rhesus monkey: concentrations and in vivo synthesis rates. Brain Res. 1979;168:133–150. [Abstract] [Google Scholar]
  • Bushnell PJ, Moser VC, MacPhail RC, Oshiro WM, Derr-Yellin EC, Phillips PM, Kodavanti PR. Neurobehavioral assessments of rats perinatally exposed to a commercial mixture of polychlorinated biphenyls. Toxicol Sci. 2002;68:109–120. [Abstract] [Google Scholar]
  • Caille I, Dumartin B, Le Moine C, Begueret J, Bloch B. Ontogeny of the D1 dopamine receptor in the rat striatonigral system: an immunohistochemical study. European Journal of Neuroscience. 1995;7:714–722. [Abstract] [Google Scholar]
  • Campbell NG, Koprich JB, Kanaan NM, Lipton JW. MDMA administration to pregnant Sprague-Dawley rats results in its passage to the fetal compartment. Neurotoxicol Teratol. 2006;28:459–465. [Abstract] [Google Scholar]
  • Cappon GD, Pu C, Vorhees CV. Time-course of methamphetamine-induced neurotoxicity in rat caudate-putamen after single-dose treatment. Brain Res. 2000;863:106–111. [Abstract] [Google Scholar]
  • Cases O, Vitalis T, Seif I, De Maeyer E, Sotelo C, Gaspar P. Lack of barrels in the somatosensory cortex of monoamine oxidase A-deficient mice: role of a serotonin excess during the critical period. Neuron. 1996;16:297–307. [Abstract] [Google Scholar]
  • Chang L, Alicata D, Ernst T, Volkow N. Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction. 2007;102(Suppl 1):16–32. [Abstract] [Google Scholar]
  • Chang L, Smith LM, LoPresti C, Yonekura ML, Kuo J, Walot I, Ernst T. Smaller subcortical volumes and cognitive deficits in children with prenatal methamphetamine exposure. Psychiatry Res. 2004;132:95–106. [Abstract] [Google Scholar]
  • Cheslack-Postava K, Fallin MD, Avramopoulos D, Connors SL, Zimmerman AW, Eberhart CG, Newschaffer CJ. beta2-Adrenergic receptor gene variants and risk for autism in the AGRE cohort. Mol Psychiatry. 2007;12:283–291. [Abstract] [Google Scholar]
  • Cho DH, Lyu HM, Lee HB, Kim PY, Chin K. Behavioral teratogenicity of methamphetamine. J Toxicol Sci. 1991;16(Suppl 1):37–49. [Abstract] [Google Scholar]
  • Clark L, Cools R, Robbins TW. The neuropsychology of ventral prefrontal cortex: decision-making and reversal learning. Brain Cogn. 2004;55:41–53. [Abstract] [Google Scholar]
  • Collette F, Van der Linden M. Brain imaging of the central executive component of working memory. Neurosci Biobehav Rev. 2002;26:105–125. [Abstract] [Google Scholar]
  • Connors SL, Crowell DE, Eberhart CG, Copeland J, Newschaffer CJ, Spence SJ, Zimmerman AW. beta2-adrenergic receptor activation and genetic polymorphisms in autism: data from dizygotic twins. J Child Neurol. 2005;20:876–884. [Abstract] [Google Scholar]
  • Connors SL, Levitt P, Matthews SG, Slotkin TA, Johnston MV, Kinney HC, Johnson WG, Dailey RM, Zimmerman AW. Fetal mechanisms in neurodevelopmental disorders. Pediatr Neurol. 2008;38:163–176. [Abstract] [Google Scholar]
  • Costa LG, Aschner M, Vitalone A, Syversen T, Soldin OP. Developmental neuropathology of environmental agents. Annu Rev Pharmacol Toxicol. 2004;44:87–110. [Europe PMC free article] [Abstract] [Google Scholar]
  • Cote F, Fligny C, Bayard E, Launay JM, Gershon MD, Mallet J, Vodjdani G. Maternal serotonin is crucial for murine embryonic development. Proc Natl Acad Sci U S A. 2007;104:329–334. [Abstract] [Google Scholar]
  • Crandall JE, Hackett HE, Tobet SA, Kosofsky BE, Bhide PG. Cocaine exposure decreases GABA neuron migration from the ganglionic eminence to the cerebral cortex in embryonic mice. Cereb Cortex. 2004;14:665–675. [Europe PMC free article] [Abstract] [Google Scholar]
  • Crandall JE, McCarthy DM, Araki KY, Sims JR, Ren JQ, Bhide PG. Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex. J Neurosci. 2007;27:3813–3822. [Europe PMC free article] [Abstract] [Google Scholar]
  • Crawford CA, Williams MT, Kohutek JL, Choi FY, Yoshida ST, McDougall SA, Vorhees CV. Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPgammaS binding in adult rats. Brain Res. 2006;1077:178–186. [Europe PMC free article] [Abstract] [Google Scholar]
  • Dannlowski U, Ohrmann P, Bauer J, Deckert J, Hohoff C, Kugel H, Arolt V, Heindel W, Kersting A, Baune BT, Suslow T. 5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression. Neuropsychopharmacology. 2008;33:418–424. [Abstract] [Google Scholar]
  • Degnan KA, Fox NA. Behavioral inhibition and anxiety disorders: multiple levels of a resilience process. Dev Psychopathol. 2007;19:729–746. [Abstract] [Google Scholar]
  • Dewar KM, Montreuil B, Grondin L, Reader TA. Dopamine D2 receptors labeled with [3H]raclopride in rat and rabbit brains. Equilibrium binding, kinetics, distribution and selectivity. Journal of Pharmacology & Experimental Therapeutics. 1989;250:696–706. [Abstract] [Google Scholar]
  • Dewar KM, Reader TA. Distribution of dopamine D1 and D2 receptors in rabbit cortical areas, hippocampus, and neostriatum in relation to dopamine contents. Synapse. 1989;4:378–386. [Abstract] [Google Scholar]
  • Dingemans MM, Ramakers GM, Gardoni F, van Kleef RG, Bergman A, Di Luca M, van den Berg M, Westerink RH, Vijverberg HP. Neonatal exposure to brominated flame retardant BDE-47 reduces long-term potentiation and postsynaptic protein levels in mouse hippocampus. Environ Health Perspect. 2007;115:865–870. [Europe PMC free article] [Abstract] [Google Scholar]
  • Dow-Edwards D, Mayes L, Spear L, Hurd Y. Cocaine and development: clinical, behavioral, and neurobiological perspectives--a symposium report. Neurotoxicol Teratol. 1999;21:481–490. [Abstract] [Google Scholar]
  • Elliott R. Executive functions and their disorders. Br Med Bull. 2003;65:49–59. [Abstract] [Google Scholar]
  • Elston GN. Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function. Cereb Cortex. 2003;13:1124–1138. [Abstract] [Google Scholar]
  • Engel SM, Berkowitz GS, Barr DB, Teitelbaum SL, Siskind J, Meisel SJ, Wetmur JG, Wolff MS. Prenatal organophosphate metabolite and organochlorine levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort. Am J Epidemiol. 2007;165:1397–1404. [Abstract] [Google Scholar]
  • Ericson JE, Crinella FM, Clarke-Stewart KA, Allhusen VD, Chan T, Robertson RT. Prenatal manganese levels linked to childhood behavioral disinhibition. Neurotoxicol Teratol. 2007;29:181–187. [Abstract] [Google Scholar]
  • Erikson KM, Dorman DC, Fitsanakis V, Lash LH, Aschner M. Alterations of oxidative stress biomarkers due to in utero and neonatal exposures of airborne manganese. Biol Trace Elem Res. 2006;111:199–215. [Abstract] [Google Scholar]
  • Erikson KM, Thompson K, Aschner J, Aschner M. Manganese neurotoxicity: a focus on the neonate. Pharmacol Ther. 2007;113:369–377. [Europe PMC free article] [Abstract] [Google Scholar]
  • Evans SM, Cone EJ, Henningfield JE. Arterial and venous cocaine plasma concentrations in humans: relationship to route of administration, cardiovascular effects and subjective effects. J Pharmacol Exp Ther. 1996;279:1345–1356. [Abstract] [Google Scholar]
  • Flores C, Manitt C, Rodaros D, Thompson KM, Rajabi H, Luk KC, Tritsch NX, Sadikot AF, Stewart J, Kennedy TE. Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine. Mol Psychiatry. 2005;10:606–612. [Abstract] [Google Scholar]
  • Forcelli PA, Heinrichs SC. Teratogenic effects of maternal antidepressant exposure on neural substrates of drug-seeking behavior in offspring. Addict Biol. 2008;13:52–62. [Abstract] [Google Scholar]
  • Francis DD, Caldji C, Champagne F, Plotsky PM, Meaney MJ. The role of corticotropin-releasing factor--norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress. Biol Psychiatry. 1999;46:1153–1166. [Abstract] [Google Scholar]
  • Friedman E, Yadin E, Wang HY. Effect of prenatal cocaine on dopamine receptor-G protein coupling in mesocortical regions of the rabbit brain. Neuroscience. 1996;70:739–747. [Abstract] [Google Scholar]
  • Gabriel M, Taylor C, Burhans L. In utero cocaine, discriminative avoidance learning with low-salient stimuli and learning-related neuronal activity in rabbits (Oryctolagus cuniculus) Behav Neurosci. 2003;117:912–926. [Abstract] [Google Scholar]
  • Galineau L, Belzung C, Kodas E, Bodard S, Guilloteau D, Chalon S. Prenatal 3,4-methylenedioxymethamphetamine (ecstasy) exposure induces long-term alterations in the dopaminergic and serotonergic functions in the rat. Brain Res Dev Brain Res. 2005;154:165–176. [Abstract] [Google Scholar]
  • Garcia SJ, Gellein K, Syversen T, Aschner M. Iron deficient and manganese supplemented diets alter metals and transporters in the developing rat brain. Toxicol Sci. 2007;95:205–214. [Abstract] [Google Scholar]
  • Gaspar P, Cases O, Maroteaux L. The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci. 2003;4:1002–1012. [Abstract] [Google Scholar]
  • Gee JR, Moser VC. Acute postnatal exposure to brominated diphenylether 47 delays neuromotor ontogeny and alters motor activity in mice. Neurotoxicol Teratol. 2008;30:79–87. [Abstract] [Google Scholar]
  • Gingras JL, O'Donnell KJ. State control in the substance-exposed fetus. I. The fetal neurobehavioral profile: an assessment of fetal state, arousal, and regulation competency. Annals of the New York Academy of Sciences. 1998;846:262–276. [Abstract] [Google Scholar]
  • Gingrich JA, Hen R. Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice. Psychopharmacology (Berl) 2001;155:1–10. [Abstract] [Google Scholar]
  • Girault JA, Greengard P. The neurobiology of dopamine signaling. Arch Neurol. 2004;61:641–644. [Abstract] [Google Scholar]
  • Goldman-Rakic PS. The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive. Philosophical Transactions of the Royal Society of London - Series B: Biological Sciences. 1996;351:1445–1453. [Abstract] [Google Scholar]
  • Goldman-Rakic PS. The cortical dopamine system: role in memory and cognition. Advances in Pharmacology (New York) 1998;42:707–711. [Abstract] [Google Scholar]
  • Goldman-Rakic PS, Lidow MS, Gallager DW. Overlap of dopaminergic, adrenergic, and serotoninergic receptors and complementarity of their subtypes in primate prefrontal cortex. Journal of Neuroscience. 1990;10:2125–2138. [Abstract] [Google Scholar]
  • Gospe SM, Jr., Zhou SS. Prenatal exposure to toluene results in abnormal neurogenesis and migration in rat somatosensory cortex. Pediatr Res. 2000;47:362–368. [Abstract] [Google Scholar]
  • Gressens P, Kosofsky BE, Evrard P. Cocaine-induced disturbances of corticogenesis in the developing murine brain. Neuroscience Letters. 1992;140:113–116. [Abstract] [Google Scholar]
  • Gross C, Zhuang X, Stark K, Ramboz S, Oosting R, Kirby L, Santarelli L, Beck S, Hen R. Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature. 2002;416:396–400. [Abstract] [Google Scholar]
  • Guerriero RM, Rajadhyaksha A, Crozatier C, Giros B, Nosten-Bertrand M, Kosofsky BE. Augmented constitutive CREB expression in the nucleus accumbens and striatum may contribute to the altered behavioral response to cocaine of adult mice exposed to cocaine in utero. Dev Neurosci. 2005;27:235–248. [Abstract] [Google Scholar]
  • Guilarte TR, McGlothan JL, Degaonkar M, Chen MK, Barker PB, Syversen T, Schneider JS. Evidence for cortical dysfunction and widespread manganese accumulation in the nonhuman primate brain following chronic manganese exposure: a 1H-MRS and MRI study. Toxicol Sci. 2006;94:351–358. [Abstract] [Google Scholar]
  • Haber SN, Ryoo H, Cox C, Lu W. Subsets of midbrain dopaminergic neurons in monkeys are distinguished by different levels of mRNA for the dopamine transporter: comparison with the mRNA for the D2 receptor, tyrosine hydroxylase and calbindin immunoreactivity. J Comp Neurol. 1995;362:400–410. [Abstract] [Google Scholar]
  • Harden TK, Wolfe BB, Sporn JR, Perkins JP, Molinoff PB. Ontogeny of beta-adrenergic receptors in rat cerebral cortex. Brain Res. 1977;125:99–108. [Abstract] [Google Scholar]
  • Hartig PR. Molecular pharmacology of serotonin receptors. Exs. 1994;71:93–102. [Abstract] [Google Scholar]
  • Harvey JA. Cocaine effects on the developing brain: current status. Neurosci Biobehav Rev. 2004;27:751–764. [Abstract] [Google Scholar]
  • Hellendall RP, Schambra UB, Liu JP, Lauder JM. Prenatal expression of 5-HT1C and 5-HT2 receptors in the rat central nervous system. Exp Neurol. 1993;120:186–201. [Abstract] [Google Scholar]
  • Herlenius E, Lagercrantz H. Development of neurotransmitter systems during critical periods. Exp Neurol. 2004;190(Suppl 1):S8–21. [Abstract] [Google Scholar]
  • Hirshfeld DR, Rosenbaum JF, Biederman J, Bolduc EA, Faraone SV, Snidman N, Reznick JS, Kagan J. Stable behavioral inhibition and its association with anxiety disorder. J Am Acad Child Adolesc Psychiatry. 1992;31:103–111. [Abstract] [Google Scholar]
  • Holmes A, le Guisquet AM, Vogel E, Millstein RA, Leman S, Belzung C. Early life genetic, epigenetic and environmental factors shaping emotionality in rodents. Neurosci Biobehav Rev. 2005;29:1335–1346. [Abstract] [Google Scholar]
  • Hougaard KS, Hass U, Lund SP, Simonsen L. Effects of prenatal exposure to toluene on postnatal development and behavior in rats. Neurotoxicol Teratol. 1999;21:241–250. [Abstract] [Google Scholar]
  • Hoyer D, Pazos A, Probst A, Palacios JM. Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Res. 1986;376:85–96. [Abstract] [Google Scholar]
  • Hsieh CT, Liang JS, Peng SS, Lee WT. Seizure associated with total parenteral nutrition-related hypermanganesemia. Pediatr Neurol. 2007;36:181–183. [Abstract] [Google Scholar]
  • Hyman SE, Malenka RC. Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci. 2001;2:695–703. [Abstract] [Google Scholar]
  • Jackson MB, Yakel JL. The 5-HT3 receptor channel. Annu Rev Physiol. 1995;57:447–468. [Abstract] [Google Scholar]
  • Jayanthi LD, Ramamoorthy S. Regulation of monoamine transporters: influence of psychostimulants and therapeutic antidepressants. Aaps J. 2005;7:E728–738. [Europe PMC free article] [Abstract] [Google Scholar]
  • Jenkins AJ, Keenan RM, Henningfield JE, Cone EJ. Correlation between pharmacological effects and plasma cocaine concentrations after smoked administration. J Anal Toxicol. 2002;26:382–392. [Abstract] [Google Scholar]
  • Johansson C, Castoldi AF, Onishchenko N, Manzo L, Vahter M, Ceccatelli S. Neurobehavioural and molecular changes induced by methylmercury exposure during development. Neurotox Res. 2007;11:241–260. [Abstract] [Google Scholar]
  • Jones L, Fischer I, Levitt P. Nonuniform alteration of dendritic development in the cerebral cortex following prenatal cocaine exposure. Cerebral Cortex. 1996;6:431–445. [Abstract] [Google Scholar]
  • Jones LB, Stanwood GD, Reinoso BS, Washington RA, Wang HY, Friedman E, Levitt P. In utero cocaine-induced dysfunction of dopamine D1 receptor signaling and abnormal differentiation of cerebral cortical neurons. Journal of Neuroscience. 2000;20:4606–4614. [Abstract] [Google Scholar]
  • Jung AB, Bennett JP., Jr. Development of striatal dopaminergic function. I. Pre- and postnatal development of mRNAs and binding sites for striatal D1 (D1a) and D2 (D2a) receptors. Brain Research. Developmental Brain Research. 1996;94:109–120. [Abstract] [Google Scholar]
  • Kafritsa Y, Fell J, Long S, Bynevelt M, Taylor W, Milla P. Long-term outcome of brain manganese deposition in patients on home parenteral nutrition. Arch Dis Child. 1998;79:263–265. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kagan J, Snidman N. Early childhood predictors of adult anxiety disorders. Biol Psychiatry. 1999;46:1536–1541. [Abstract] [Google Scholar]
  • Kagan J, Snidman N, Kahn V, Towsley S. The preservation of two infant temperaments into adolescence. Monogr Soc Res Child Dev. 2007;72:1–75, vii. discussion 76-91. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry. 2005;162:1403–1413. [Abstract] [Google Scholar]
  • Karmel BZ, Gardner JM. Prenatal cocaine exposure effects on arousal-modulated attention during the neonatal period. Developmental Psychobiology. 1996;29:463–480. [Abstract] [Google Scholar]
  • Kasirsky G. Teratogenic effects of methamphetamine in mice and rabbits. J Am Osteopath Assoc. 1971;70:1119–1120. [Abstract] [Google Scholar]
  • Kebabian JW, Calne DB. Multiple receptors for dopamine. Nature. 1979;277:93–96. [Abstract] [Google Scholar]
  • Kellendonk C, Simpson EH, Polan HJ, Malleret G, Vronskaya S, Winiger V, Moore H, Kandel ER. Transient and Selective Overexpression of Dopamine D2 Receptors in the Striatum Causes Persistent Abnormalities in Prefrontal Cortex Functioning. Neuron. 2006;49:603–615. [Abstract] [Google Scholar]
  • Kim H, Lim SW, Kim S, Kim JW, Chang YH, Carroll BJ, Kim DK. Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression. Jama. 2006;296:1609–1618. [Abstract] [Google Scholar]
  • Kiyatkin EA. Functional significance of mesolimbic dopamine. Neuroscience and Biobehavioral Reviews. 1995;19:573–598. [Abstract] [Google Scholar]
  • Koprich JB, Chen EY, Kanaan NM, Campbell NG, Kordower JH, Lipton JW. Prenatal 3,4-methylenedioxymethamphetamine (ecstasy) alters exploratory behavior, reduces monoamine metabolism, and increases forebrain tyrosine hydroxylase fiber density of juvenile rats. Neurotoxicol Teratol. 2003;25:509–517. [Abstract] [Google Scholar]
  • Kuchiiwa S, Cheng SB, Nagatomo I, Akasaki Y, Uchida M, Tominaga M, Hashiguchi W, Kuchiiwa T. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin decreases serotonin-immunoreactive neurons in raphe nuclei of male mouse offspring. Neurosci Lett. 2002;317:73–76. [Abstract] [Google Scholar]
  • Lambe EK, Krimer LS, Goldman-Rakic PS. Differential postnatal development of catecholamine and serotonin inputs to identified neurons in prefrontal cortex of rhesus monkey. J Neurosci. 2000;20:8780–8787. [Abstract] [Google Scholar]
  • Lauder J, Bloom F. Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei, and substantia nigra of the rat. I. Cell differentiation. Journal of Comparative Neurology. 1974a;155:469–482. [Abstract] [Google Scholar]
  • Lauder JM, Bloom FE. Ontogeny of monoamine neurons in the locus coeruleus, Raphe nuclei and substantia nigra of the rat. I. Cell differentiation. J Comp Neurol. 1974b;155:469–481. [Abstract] [Google Scholar]
  • Lauder JM, Bloom FE. Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat. II. Synaptogenesis. J Comp Neurol. 1975;163:251–264. [Abstract] [Google Scholar]
  • Laviola G, Gioiosa L, Adriani W, Palanza P. D-amphetamine-related reinforcing effects are reduced in mice exposed prenatally to estrogenic endocrine disruptors. Brain Res Bull. 2005;65:235–240. [Abstract] [Google Scholar]
  • Lebrand C, Cases O, Adelbrecht C, Doye A, Alvarez C, El Mestikawy S, Seif I, Gaspar P. Transient uptake and storage of serotonin in developing thalamic neurons. Neuron. 1996;17:823–835. [Abstract] [Google Scholar]
  • Lee CT, Chen J, Hayashi T, Tsai SY, Sanchez JF, Errico SL, Amable R, Su TP, Lowe RH, Huestis MA, Shen J, Becker KG, Geller HM, Freed WJ. A mechanism for the inhibition of neural progenitor cell proliferation by cocaine. PLoS Med. 2008;5:e117. [Europe PMC free article] [Abstract] [Google Scholar]
  • Lee JW. Manganese intoxication. Arch Neurol. 2000;57:597–599. [Abstract] [Google Scholar]
  • Levin ED, Addy N, Baruah A, Elias A, Christopher NC, Seidler FJ, Slotkin TA. Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations. Neurotoxicol Teratol. 2002;24:733–741. [Abstract] [Google Scholar]
  • Levitt P, Moore RY. Noradrenaline neuron innervation of the neocortex in the rat. Brain Research. 1978;139:219–231. [Abstract] [Google Scholar]
  • Levitt P, Moore RY. Development of the noradrenergic innervation of neocortex. Brain Research. 1979;162:243–259. [Abstract] [Google Scholar]
  • Levitt P, Rakic P. The time of genesis, embryonic origin and differentiation of the brain stem monoamine neurons in the rhesus monkey. Brain Research. 1982;256:35–57. [Abstract] [Google Scholar]
  • Levitt P, Rakic P, Goldman-Rakic P. Region-specific distribution of catecholamine afferents in primate cerebral cortex: a fluorescence histochemical analysis. Journal of Comparative Neurology. 1984;227:23–36. [Abstract] [Google Scholar]
  • Lidov HG, Molliver ME. Immunohistochemical study of the development of serotonergic neurons in the rat CNS. Brain Res Bull. 1982;9:559–604. [Abstract] [Google Scholar]
  • Lidow MS. D1- and D2 dopaminergic receptors in the developing cerebral cortex of macaque monkey: a film autoradiographic study. Neuroscience. 1995a;65:439–452. [Abstract] [Google Scholar]
  • Lidow MS. Prenatal cocaine exposure adversely affects development of the primate cerebral cortex. Synapse. 1995b;21:332–341. [Abstract] [Google Scholar]
  • Lidow MS. Consequences of prenatal cocaine exposure in nonhuman primates. Brain Res Dev Brain Res. 2003;147:23–36. [Abstract] [Google Scholar]
  • Lidow MS, Goldman-Rakic PS, Gallager DW, Rakic P. Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative autoradiographic analysis using [3H]raclopride, [3H]spiperone and [3H]SCH23390. Neuroscience. 1991;40:657–671. [Abstract] [Google Scholar]
  • Lidow MS, Song ZM. Primates exposed to cocaine in utero display reduced density and number of cerebral cortical neurons. J Comp Neurol. 2001;435:263–275. [Abstract] [Google Scholar]
  • Lin L, Isacson O. Axonal growth regulation of fetal and embryonic stem cell-derived dopaminergic neurons by Netrin-1 and Slits. Stem Cells. 2006;24:2504–2513. [Europe PMC free article] [Abstract] [Google Scholar]
  • Linares TJ, Singer LT, Kirchner HL, Short EJ, Min MO, Hussey P, Minnes S. Mental health outcomes of cocaine-exposed children at 6 years of age. J Pediatr Psychol. 2006;31:85–97. [Europe PMC free article] [Abstract] [Google Scholar]
  • Lindvall O, Bjorkland A, Divac I. Organization of catecholamine neurons projecting to the frontal cortex of the rat. Brain Research. 1978;142:1–24. [Abstract] [Google Scholar]
  • Ljung K, Vahter M. Time to re-evaluate the guideline value for manganese in drinking water? Environ Health Perspect. 2007;115:1533–1538. [Europe PMC free article] [Abstract] [Google Scholar]
  • Llansola M, Erceg S, Monfort P, Montoliu C, Felipo V. Prenatal exposure to polybrominated diphenylether 99 enhances the function of the glutamate-nitric oxide-cGMP pathway in brain in vivo and in cultured neurons. Eur J Neurosci. 2007;25:373–379. [Abstract] [Google Scholar]
  • Lu C, Barr DB, Pearson MA, Waller LA. Dietary intake and its contribution to longitudinal organophosphorus pesticide exposure in urban/suburban children. Environ Health Perspect. 2008;116:537–542. [Europe PMC free article] [Abstract] [Google Scholar]
  • Lucki I. The spectrum of behaviors influenced by serotonin. Biol Psychiatry. 1998;44:151–162. [Abstract] [Google Scholar]
  • Lyles J, Cadet JL. Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms. Brain Res Brain Res Rev. 2003;42:155–168. [Abstract] [Google Scholar]
  • Lynd-Balta E, Haber SN. The organization of midbrain projections to the striatum in the primate: sensorimotor-related striatum versus ventral striatum. Neuroscience. 1994a;59:625–640. [Abstract] [Google Scholar]
  • Lynd-Balta E, Haber SN. The organization of midbrain projections to the ventral striatum in the primate. Neuroscience. 1994b;59:609–623. [Abstract] [Google Scholar]
  • Malanga CJ, Kosofsky BE. Does drug abuse beget drug abuse? Behavioral analysis of addiction liability in animal models of prenatal drug exposure. Brain Res Dev Brain Res. 2003;147:47–57. [Abstract] [Google Scholar]
  • Malanga CJ, Riday TT, Carlezon WA, Jr., Kosofsky BE. Prenatal exposure to cocaine increases the rewarding potency of cocaine and selective dopaminergic agonists in adult mice. Biol Psychiatry. 2008;63:214–221. [Europe PMC free article] [Abstract] [Google Scholar]
  • Maschi S, Clavenna A, Campi R, Schiavetti B, Bernat M, Bonati M. Neonatal outcome following pregnancy exposure to antidepressants: a prospective controlled cohort study. Bjog. 2008;115:283–289. [Abstract] [Google Scholar]
  • Mayes L, Snyder PJ, Langlois E, Hunter N. Visuospatial working memory in school-aged children exposed in utero to cocaine. Child Neuropsychol. 2007;13:205–218. [Abstract] [Google Scholar]
  • Mayes LC. A behavioral teratogenic model of the impact of prenatal cocaine exposure on arousal regulatory systems. Neurotoxicol Teratol. 2002;24:385–395. [Abstract] [Google Scholar]
  • Mayes LC, Cicchetti D, Acharyya S, Zhang H. Developmental trajectories of cocaine-and-other-drug-exposed and non-cocaine-exposed children. J Dev Behav Pediatr. 2003;24:323–335. [Abstract] [Google Scholar]
  • McCann D, Barrett A, Cooper A, Crumpler D, Dalen L, Grimshaw K, Kitchin E, Lok K, Porteous L, Prince E, Sonuga-Barke E, Warner JO, Stevenson J. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet. 2007;370:1560–1567. [Abstract] [Google Scholar]
  • McElhatton PR, Bateman DN, Evans C, Pughe KR, Thomas SH. Congenital anomalies after prenatal ecstasy exposure. Lancet. 1999;354:1441–1442. [Abstract] [Google Scholar]
  • Melo P, Moreno VZ, Vazquez SP, Pinazo-Duran MD, Tavares MA. Myelination changes in the rat optic nerve after prenatal exposure to methamphetamine. Brain Res. 2006;1106:21–29. [Abstract] [Google Scholar]
  • Melo P, Pinazo-Duran MD, Salgado-Borges J, Tavares MA. Correlation of axon size and myelin occupancy in rats prenatally exposed to methamphetamine. Brain Res. 2008;1222:61–68. [Abstract] [Google Scholar]
  • Meyer A, Seidler FJ, Aldridge JE, Slotkin TA. Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos. Toxicol Appl Pharmacol. 2005;203:154–166. [Abstract] [Google Scholar]
  • Missale C, Nash SR, Robinson SW, Jaber M, Caron MG. Dopamine receptors: from structure to function. Physiological Reviews. 1998;78:189–225. [Abstract] [Google Scholar]
  • Miyagawa K, Narita M, Narita M, Niikura K, Akama H, Tsurukawa Y, Suzuki T. Changes in central dopaminergic systems with the expression of Shh or GDNF in mice perinatally exposed to bisphenol-A. Nihon Shinkei Seishin Yakurigaku Zasshi. 2007;27:69–75. [Abstract] [Google Scholar]
  • Moran-Gates T, Gan L, Park YS, Zhang K, Baldessarini RJ, Tarazi FI. Repeated antipsychotic drug exposure in developing rats: dopamine receptor effects. Synapse. 2006;59:92–100. [Abstract] [Google Scholar]
  • Moreno M, Canadas F, Cardona D, Sunol C, Campa L, Sanchez-Amate MC, Flores P, Sanchez-Santed F. Long-term monoamine changes in the striatum and nucleus accumbens after acute chlorpyrifos exposure. Toxicol Lett. 2008;176:162–167. [Abstract] [Google Scholar]
  • Morford LL, Inman-Wood SL, Gudelsky GA, Williams MT, Vorhees CV. Impaired spatial and sequential learning in rats treated neonatally with D-fenfluramine. Eur J Neurosci. 2002;16:491–500. [Abstract] [Google Scholar]
  • Morilak DA, Ciaranello RD. Ontogeny of 5-hydroxytryptamine2 receptor immunoreactivity in the developing rat brain. Neuroscience. 1993;55:869–880. [Abstract] [Google Scholar]
  • Morris MJ, Dausse JP, Devynck MA, Meyer P. Ontogeny of alpha 1 and alpha 2-adrenoceptors in rat brain. Brain Res. 1980;190:268–271. [Abstract] [Google Scholar]
  • Morrow BA, Elsworth JD, Roth RH. Prenatal cocaine exposure disrupts non-spatial, short-term memory in adolescent and adult male rats. Behav Brain Res. 2002;129:217–223. [Abstract] [Google Scholar]
  • Moser VC. Animal models of chronic pesticide neurotoxicity. Hum Exp Toxicol. 2007;26:321–331. [Abstract] [Google Scholar]
  • Murphy DL, Lesch KP. Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci. 2008;9:85–96. [Abstract] [Google Scholar]
  • Murphy EH, Fischer I, Friedman E, Grayson D, Jones L, Levitt P, O'Brien-Jenkins A, Wang HY, Wang XH. Cocaine administration in pregnant rabbits alters cortical structure and function in their progeny in the absence of maternal seizures. Experimental Brain Research. 1997;114:433–441. [Abstract] [Google Scholar]
  • Nagatomo S, Umehara F, Hanada K, Nobuhara Y, Takenaga S, Arimura K, Osame M. Manganese intoxication during total parenteral nutrition: report of two cases and review of the literature. J Neurol Sci. 1999;162:102–105. [Abstract] [Google Scholar]
  • Nasif FJ, Cuadra GR, Ramirez OA. Permanent alteration of central noradrenergic system by prenatally administered amphetamine. Brain Res Dev Brain Res. 1999;112:181–188. [Abstract] [Google Scholar]
  • Nasuti C, Gabbianelli R, Falcioni ML, Di Stefano A, Sozio P, Cantalamessa F. Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids. Toxicology. 2007;229:194–205. [Abstract] [Google Scholar]
  • Nestler EJ. Neurobiology. Total recall-the memory of addiction. Science. 2001;292:2266–2267. [Abstract] [Google Scholar]
  • Nora JJ, Trasler DG, Fraser FC. Malformations in mice induced by dexamphetamine sulphate. Lancet. 1965;2:1021–1022. [Abstract] [Google Scholar]
  • Normandin L, Panisset M, Zayed J. Manganese neurotoxicity: behavioral, pathological, and biochemical effects following various routes of exposure. Rev Environ Health. 2002;17:189–217. [Abstract] [Google Scholar]
  • Novikova SI, He F, Bai J, Cutrufello NJ, Lidow MS, Undieh AS. Maternal cocaine administration in mice alters DNA methylation and gene expression in hippocampal neurons of neonatal and prepubertal offspring. PLoS ONE. 2008;3:e1919. [Europe PMC free article] [Abstract] [Google Scholar]
  • Nowak P, Szczerbak G, Nitka D, Kostrzewa RM, Sitkiewicz T, Brus R. Effect of prenatal lead exposure on nigrostriatal neurotransmission and hydroxyl radical formation in rat neostriatum: Dopaminergic-nitrergic interaction. Toxicology. 2008 [Abstract] [Google Scholar]
  • Oberlander TF, Bonaguro RJ, Misri S, Papsdorf M, Ross CJ, Simpson EM. Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications. Mol Psychiatry. 2008;13:65–73. [Abstract] [Google Scholar]
  • Ohtani N, Goto T, Waeber C, Bhide PG. Dopamine modulates cell cycle in the lateral ganglionic eminence. J Neurosci. 2003;23:2840–2850. [Europe PMC free article] [Abstract] [Google Scholar]
  • Olivier B, Mos J, van Oorschot R, Hen R. Serotonin receptors and animal models of aggressive behavior. Pharmacopsychiatry. 1995;28(Suppl 2):80–90. [Abstract] [Google Scholar]
  • Olney JW, Wozniak DF, Farber NB, Jevtovic-Todorovic V, Bittigau P, Ikonomidou C. The enigma of fetal alcohol neurotoxicity. Ann Med. 2002;34:109–119. [Abstract] [Google Scholar]
  • Olson L, Seiger A. Early prenatal ontogeny of central monoamine neurons in the rat: fluorescence histochemical observations. Zeitschrift fur Anatomie und Entwicklungsgeschichte. 1972;137:301–316. [Abstract] [Google Scholar]
  • Olson L, Seiger A, Fuxe K. Heterogeneity of striatal and limbic dopamine innervation: highly fluorescent islands in developing and adult rats. Brain Res. 1972;44:283–288. [Abstract] [Google Scholar]
  • Pappas BA, Zhang D, Davidson CM, Crowder T, Park GA, Fortin T. Perinatal manganese exposure: behavioral, neurochemical, and histopathological effects in the rat. Neurotoxicol Teratol. 1997;19:17–25. [Abstract] [Google Scholar]
  • Parlaman JP, Thompson BL, Levitt P, Stanwood GD. Pharmacokinetic profile of cocaine following intravenous administration in the female rabbit. Eur J Pharmacol. 2007;563:124–129. [Europe PMC free article] [Abstract] [Google Scholar]
  • Pearson KH, Nonacs RM, Viguera AC, Heller VL, Petrillo LF, Brandes M, Hennen J, Cohen LS. Birth outcomes following prenatal exposure to antidepressants. J Clin Psychiatry. 2007;68:1284–1289. [Abstract] [Google Scholar]
  • Persico AM, Di Pino G, Levitt P. Multiple receptors mediate the trophic effects of serotonin on ventroposterior thalamic neurons in vitro. Brain Res. 2006;1095:17–25. [Abstract] [Google Scholar]
  • Piper BJ. A developmental comparison of the neurobehavioral effects of ecstasy (MDMA) Neurotoxicol Teratol. 2007;29:288–300. [Europe PMC free article] [Abstract] [Google Scholar]
  • Pittman RN, Minneman KP, Molinoff PB. Ontogeny of beta 1- and beta 2-adrenergic receptors in rat cerebellum and cerebral cortex. Brain Res. 1980;188:357–368. [Abstract] [Google Scholar]
  • Plessinger MA. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy. Obstet Gynecol Clin North Am. 1998;25:119–138. [Abstract] [Google Scholar]
  • Pranzatelli MR. Regional differences in the ontogeny of 5-hydroxytryptamine-1C binding sites in rat brain and spinal cord. Neurosci Lett. 1993;149:9–11. [Abstract] [Google Scholar]
  • Rao PA, Molinoff PB, Joyce JN. Ontogeny of dopamine D1 and D2 receptor subtypes in rat basal ganglia: a quantitative autoradiographic study. Developmental Brain Research. 1991;60:161–177. [Abstract] [Google Scholar]
  • Rauh VA, Garfinkel R, Perera FP, Andrews HF, Hoepner L, Barr DB, Whitehead R, Tang D, Whyatt RW. Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics. 2006;118:e1845–1859. [Europe PMC free article] [Abstract] [Google Scholar]
  • Reader TA, Dewar KM, Grondin L. Distribution of monoamines and metabolites in rabbit neostriatum, hippocampus and cortex. Brain Research Bulletin. 1989a;23:237–247. [Abstract] [Google Scholar]
  • Reader TA, Grondin L, Montreuil B, Dewar KM. Dopamine D1 receptors labelled with [3H]SCH23390 in rabbit cerebral cortex and neostriatum. Equilibrium binding, kinetics and selectivity. Naunyn-Schmiedebergs Archives of Pharmacology. 1989b;340:617–625. [Abstract] [Google Scholar]
  • Rebsam A, Seif I, Gaspar P. Refinement of thalamocortical arbors and emergence of barrel domains in the primary somatosensory cortex: a study of normal and monoamine oxidase a knock-out mice. J Neurosci. 2002;22:8541–8552. [Abstract] [Google Scholar]
  • Reichel CM, Wacan JJ, Farley CM, Stanley BJ, Crawford CA, McDougall SA. Postnatal manganese exposure attenuates cocaine-induced locomotor activity and reduces dopamine transporters in adult male rats. Neurotoxicol Teratol. 2006;28:323–332. [Abstract] [Google Scholar]
  • Reinoso BS, Undie AS, Levitt P. Dopamine receptors mediate differential morphological effects on cerebral cortical neurons in vitro. Journal of Neuroscience Research. 1996;43:439–453. [Abstract] [Google Scholar]
  • Ren JQ, Malanga CJ, Tabit E, Kosofsky BE. Neuropathological consequences of prenatal cocaine exposure in the mouse. Int J Dev Neurosci. 2004;22:309–320. [Europe PMC free article] [Abstract] [Google Scholar]
  • Rhodes MC, Seidler FJ, Abdel-Rahman A, Tate CA, Nyska A, Rincavage HL, Slotkin TA. Terbutaline is a developmental neurotoxicant: effects on neuroproteins and morphology in cerebellum, hippocampus, and somatosensory cortex. J Pharmacol Exp Ther. 2004;308:529–537. [Abstract] [Google Scholar]
  • Richardson GA, Conroy ML, Day NL. Prenatal cocaine exposure: effects on the development of school-age children. Neurotoxicology & Teratology. 1996;18:627–634. [Abstract] [Google Scholar]
  • Richardson JR, Caudle WM, Wang M, Dean ED, Pennell KD, Miller GW. Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson's disease. Faseb J. 2006;20:1695–1697. [Abstract] [Google Scholar]
  • Rocha BA, Mead AN, Kosofsky BE. Increased vulnerability to self-administer cocaine in mice prenatally exposed to cocaine. Psychopharmacology (Berl) 2002;163:221–229. [Abstract] [Google Scholar]
  • Rodier PM. Environmental causes of central nervous system maldevelopment. Pediatrics. 2004;113:1076–1083. [Abstract] [Google Scholar]
  • Roegge CS, Timofeeva OA, Seidler FJ, Slotkin TA, Levin ED. Developmental diazinon neurotoxicity in rats: later effects on emotional response. Brain Res Bull. 2008;75:166–172. [Europe PMC free article] [Abstract] [Google Scholar]
  • Romano AG, Harvey JA. Elicitation and modification of the rabbit's nictitating membrane reflex following prenatal exposure to cocaine. Pharmacol Biochem Behav. 1996;53:857–862. [Abstract] [Google Scholar]
  • Rosenbaum JF, Biederman J, Bolduc-Murphy EA, Faraone SV, Chaloff J, Hirshfeld DR, Kagan J. Behavioral inhibition in childhood: a risk factor for anxiety disorders. Harv Rev Psychiatry. 1993;1:2–16. [Abstract] [Google Scholar]
  • Rosengarten H, Friedhoff AJ. Enduring changes in dopamine receptor cells of pups from drug administration to pregnant and nursing rats. Science. 1979;203:1133–1135. [Abstract] [Google Scholar]
  • Rosengarten H, Quartermain D. Effect of prenatal administration of haloperidol, risperidone, quetiapine and olanzapine on spatial learning and retention in adult rats. Pharmacol Biochem Behav. 2002;72:575–579. [Abstract] [Google Scholar]
  • Sales N, Martres MP, Bouthenet ML, Schwartz JC. Ontogeny of dopaminergic D-2 receptors in the rat nervous system: characterization and detailed autoradiographic mapping with [125I]iodosulpride. Neuroscience. 1989;28:673–700. [Abstract] [Google Scholar]
  • Scalzo FM, Ali SF, Holson RR, Williams RL. Haloperidol effects on the developing dopamine system: conflicting results and implications for neurobehavioral teratology research. Ann Ist Super Sanita. 1993;29:139–146. [Abstract] [Google Scholar]
  • Scalzo FM, Spear LP. Chronic haloperidol during development attenuates dopamine autoreceptor function in striatal and mesolimbic brain regions of young and older adult rats. Psychopharmacology (Berl) 1985;85:271–276. [Abstract] [Google Scholar]
  • Schaefer TL, Skelton MR, Herring NR, Gudelsky GA, Vorhees CV, Williams MT. Short- and long-term effects of (+)-methamphetamine and (+/−)-3,4-methylenedioxymethamphetamine on monoamine and corticosterone levels in the neonatal rat following multiple days of treatment. J Neurochem. 2008;104:1674–1685. [Europe PMC free article] [Abstract] [Google Scholar]
  • Schambra UB, Duncan GE, Breese GR, Fornaretto MG, Caron MG, Fremeau RT., Jr. Ontogeny of D1A and D2 dopamine receptor subtypes in rat brain using in situ hybridization and receptor binding. Neuroscience. 1994;62:65–85. [Abstract] [Google Scholar]
  • Schwartz CE, Snidman N, Kagan J. Adolescent social anxiety as an outcome of inhibited temperament in childhood. J Am Acad Child Adolesc Psychiatry. 1999;38:1008–1015. [Abstract] [Google Scholar]
  • Segal M, Pickel V, Bloom F. The projections of the nucleus locus coeruleus: an autoradiographic study. Life Sci. 1973;13:817–821. [Abstract] [Google Scholar]
  • Simansky KJ, Baker G, Kachelries WJ, Hood H, Romano AG, Harvey JA. Prenatal exposure to cocaine reduces dopaminergic D1-mediated motor function but spares the enhancement of learning by amphetamine in rabbits. Annals of the New York Academy of Sciences. 1998;846:375–378. [Abstract] [Google Scholar]
  • Simansky KJ, Kachelries WJ. Prenatal exposure to cocaine selectively disrupts motor responding to D-amphetamine in young and mature rabbits. Neuropharmacology. 1996;35:71–78. [Abstract] [Google Scholar]
  • Singer LT, Minnes S, Short E, Arendt R, Farkas K, Lewis B, Klein N, Russ S, Min MO, Kirchner HL. Cognitive outcomes of preschool children with prenatal cocaine exposure. Jama. 2004;291:2448–2456. [Abstract] [Google Scholar]
  • Singer LT, Nelson S, Short E, Min MO, Lewis B, Russ S, Minnes S. Prenatal cocaine exposure: drug and environmental effects at 9 years. J Pediatr. 2008;153:105–111. [Europe PMC free article] [Abstract] [Google Scholar]
  • Singh KP, Singh M. Effect of single prenatal haloperidol exposure on hippocampus and striatum of developing rat brain. Indian J Exp Biol. 2001;39:223–229. [Abstract] [Google Scholar]
  • Singh KP, Singh M. Effect of prenatal haloperidol exposure on behavioral alterations in rats. Neurotoxicol Teratol. 2002;24:497–502. [Abstract] [Google Scholar]
  • Skelton MR, Williams MT, Vorhees CV. Developmental effects of 3,4-methylenedioxymethamphetamine: a review. Behav Pharmacol. 2008;19:91–111. [Europe PMC free article] [Abstract] [Google Scholar]
  • Slamberova R, Bernaskova K, Matejovska I, Schutova B. Does prenatal methamphetamine exposure affect seizure susceptibility in adult rats with acute administration of the same drug? Epilepsy Res. 2008;78:33–39. [Abstract] [Google Scholar]
  • Slotkin TA. Fetal nicotine or cocaine exposure: which one is worse? Journal of Pharmacology & Experimental Therapeutics. 1998;285:931–945. [Abstract] [Google Scholar]
  • Slotkin TA. Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates. Toxicol Appl Pharmacol. 2004;198:132–151. [Abstract] [Google Scholar]
  • Slotkin TA, Kudlacz EM, Lappi SE, Tayyeb MI, Seidler FJ. Fetal terbutaline exposure causes selective postnatal increases in cerebellar alpha-adrenergic receptor binding. Life Sci. 1990;47:2051–2057. [Abstract] [Google Scholar]
  • Slotkin TA, Levin ED, Seidler FJ. Comparative developmental neurotoxicity of organophosphate insecticides: effects on brain development are separable from systemic toxicity. Environ Health Perspect. 2006;114:746–751. [Europe PMC free article] [Abstract] [Google Scholar]
  • Slotkin TA, Seidler FJ. Developmental exposure to terbutaline and chlorpyrifos, separately or sequentially, elicits presynaptic serotonergic hyperactivity in juvenile and adolescent rats. Brain Res Bull. 2007a;73:301–309. [Europe PMC free article] [Abstract] [Google Scholar]
  • Slotkin TA, Seidler FJ. Prenatal chlorpyrifos exposure elicits presynaptic serotonergic and dopaminergic hyperactivity at adolescence: critical periods for regional and sex-selective effects. Reprod Toxicol. 2007b;23:421–427. [Abstract] [Google Scholar]
  • Slotkin TA, Tate CA, Cousins MM, Seidler FJ. Beta-adrenoceptor signaling in the developing brain: sensitization or desensitization in response to terbutaline. Brain Res Dev Brain Res. 2001;131:113–125. [Abstract] [Google Scholar]
  • Smith L, Yonekura ML, Wallace T, Berman N, Kuo J, Berkowitz C. Effects of prenatal methamphetamine exposure on fetal growth and drug withdrawal symptoms in infants born at term. J Dev Behav Pediatr. 2003;24:17–23. [Abstract] [Google Scholar]
  • Smith LM, Chang L, Yonekura ML, Grob C, Osborn D, Ernst T. Brain proton magnetic resonance spectroscopy in children exposed to methamphetamine in utero. Neurology. 2001;57:255–260. [Abstract] [Google Scholar]
  • Smith LM, LaGasse LL, Derauf C, Grant P, Shah R, Arria A, Huestis M, Haning W, Strauss A, Della Grotta S, Liu J, Lester BM. The infant development, environment, and lifestyle study: effects of prenatal methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth. Pediatrics. 2006;118:1149–1156. [Abstract] [Google Scholar]
  • Smith LM, Lagasse LL, Derauf C, Grant P, Shah R, Arria A, Huestis M, Haning W, Strauss A, Grotta SD, Fallone M, Liu J, Lester BM. Prenatal methamphetamine use and neonatal neurobehavioral outcome. Neurotoxicol Teratol. 2008;30:20–28. [Europe PMC free article] [Abstract] [Google Scholar]
  • Song ZM, Undie AS, Koh PO, Fang YY, Zhang L, Dracheva S, Sealfon SC, Lidow MS. D1 dopamine receptor regulation of microtubule-associated protein-2 phosphorylation in developing cerebral cortical neurons. J Neurosci. 2002;22:6092–6105. [Abstract] [Google Scholar]
  • Stanwood GD, Levitt P. The effects of cocaine on the developing nervous system. In: Nelson CA, Luciana M, editors. Handbook of Developmental Cognitive Neuroscience. MIT Press; 2001. pp. 519–536. [Google Scholar]
  • Stanwood GD, Levitt P. Repeated i.v. cocaine exposure produces long-lasting behavioral sensitization in pregnant adults, but behavioral tolerance in their offspring. Neuroscience. 2003;122:579–583. [Abstract] [Google Scholar]
  • Stanwood GD, Levitt P. Drug exposure early in life: functional repercussions of changing neuropharmacology during sensitive periods of brain development. Current Opinion in Pharmacology. 2004;4:65–71. [Abstract] [Google Scholar]
  • Stanwood GD, Levitt P. Prenatal exposure to cocaine produces unique developmental and long-term adaptive changes in dopamine D1 receptor activity and subcellular distribution. J Neurosci. 2007;27:152–157. [Abstract] [Google Scholar]
  • Stanwood GD, Parlaman JP, Levitt P. Anatomical abnormalities in dopaminoceptive regions of the cerebral cortex of dopamine D(1) receptor mutant mice. J Comp Neurol. 2005;487:270–282. [Abstract] [Google Scholar]
  • Stanwood GD, Parlaman JP, Levitt P. Genetic or pharmacological inactivation of the dopamine D1 receptor differentially alters the expression of regulator of G-protein signalling (Rgs) transcripts. Eur J Neurosci. 2006;24:806–818. [Abstract] [Google Scholar]
  • Stanwood GD, Washington RA, Levitt P. Identification of a sensitive period of prenatal cocaine exposure that alters the development of the anterior cingulate cortex. Cerebral Cortex. 2001a;11:430–440. [Abstract] [Google Scholar]
  • Stanwood GD, Washington RA, Shumsky JS, Levitt P. Prenatal cocaine exposure produces consistent developmental alterations in dopamine-rich regions of the cerebral cortex. Neuroscience. 2001b;106:5–14. [Abstract] [Google Scholar]
  • Sundstrom E, Kolare S, Souverbie F, Samuelsson EB, Pschera H, Lunell NO, Seiger A. Neurochemical differentiation of human bulbospinal monoaminergic neurons during the first trimester. Brain Res Dev Brain Res. 1993;75:1–12. [Abstract] [Google Scholar]
  • Suzuki T, Mizuo K, Miyagawa K, Narita M. [Exposure to bisphenol-A affects the rewarding system in mice] Nihon Shinkei Seishin Yakurigaku Zasshi. 2005;25:125–128. [Abstract] [Google Scholar]
  • Suzuki T, Mizuo K, Nakazawa H, Funae Y, Fushiki S, Fukushima S, Shirai T, Narita M. Prenatal and neonatal exposure to bisphenol-A enhances the central dopamine D1 receptor-mediated action in mice: enhancement of the methamphetamine-induced abuse state. Neuroscience. 2003;117:639–644. [Abstract] [Google Scholar]
  • Szczerbak G, Nowak P, Kostrzewa RM, Brus R. Maternal lead exposure produces long-term enhancement of dopaminergic reactivity in rat offspring. Neurochem Res. 2007;32:1791–1798. [Abstract] [Google Scholar]
  • Tavares MA, Silva MC, Silva-Araujo A, Xavier MR, Ali SF. Effects of prenatal exposure to amphetamine in the medial prefrontal cortex of the rat. Int J Dev Neurosci. 1996;14:585–596. [Abstract] [Google Scholar]
  • Thompson B, Stanwood G, Levitt P. Society For Neuroscience. Washington, DC: 2005a. Double dissociation of the reinforcing properties of cocaine. [Google Scholar]
  • Thompson BL, Levitt P, Stanwood GD. Prenatal cocaine exposure specifically alters spontaneous alternation behavior. Behav Brain Res. 2005b;164:107–116. [Abstract] [Google Scholar]
  • Todd RD. Neural development is regulated by classical neurotransmitters: dopamine D2 receptor stimulation enhances neurite outgrowth. Biological Psychiatry. 1992;31:794–807. [Abstract] [Google Scholar]
  • Tran TT, Chowanadisai W, Crinella FM, Chicz-DeMet A, Lonnerdal B. Effect of high dietary manganese intake of neonatal rats on tissue mineral accumulation, striatal dopamine levels, and neurodevelopmental status. Neurotoxicology. 2002;23:635–643. [Abstract] [Google Scholar]
  • Vorhees CV, Inman-Wood SL, Morford LL, Broening HW, Fukumura M, Moran MS. Adult learning deficits after neonatal exposure to D-methamphetamine: selective effects on spatial navigation and memory. J Neurosci. 2000;20:4732–4739. [Abstract] [Google Scholar]
  • Vorhees CV, Skelton MR, Williams MT. Age-dependent effects of neonatal methamphetamine exposure on spatial learning. Behav Pharmacol. 2007;18:549–562. [Europe PMC free article] [Abstract] [Google Scholar]
  • Walderhaug E, Magnusson A, Neumeister A, Lappalainen J, Lunde H, Refsum H, Landro NI. Interactive effects of sex and 5-HTTLPR on mood and impulsivity during tryptophan depletion in healthy people. Biol Psychiatry. 2007;62:593–599. [Abstract] [Google Scholar]
  • Wang HY, Runyan S, Yadin E, Friedman E. Prenatal exposure to cocaine selectively reduces D1 dopamine receptor-mediated activation of striatal Gs proteins. Journal of Pharmacology & Experimental Therapeutics. 1995a;273:492–498. [Abstract] [Google Scholar]
  • Wang JH, Yang JZ, Wilson FA, Ma YY. Differently lasting effects of prenatal and postnatal chronic clozapine/haloperidol on activity and memory in mouse offspring. Pharmacol Biochem Behav. 2006;84:468–478. [Abstract] [Google Scholar]
  • Wang XH, Levitt P, Grayson DR, Murphy EH. Intrauterine cocaine exposure of rabbits: persistent elevation of GABA-immunoreactive neurons in anterior cingulate cortex but not visual cortex. Brain Research. 1995b;689:32–46. [Abstract] [Google Scholar]
  • Wang XH, Levitt P, O'Brien Jenkins A, Murphy EH. Normal development of tyrosine hydroxylase and serotonin immunoreactive fibers innervating anterior cingulate cortex and visual cortex in rabbits exposed prenatally to cocaine. Brain Research. 1996;715:221–224. [Abstract] [Google Scholar]
  • Wasserman GA, Liu X, Parvez F, Ahsan H, Levy D, Factor-Litvak P, Kline J, van Geen A, Slavkovich V, LoIacono NJ, Cheng Z, Zheng Y, Graziano JH. Water manganese exposure and children's intellectual function in Araihazar, Bangladesh. Environ Health Perspect. 2006;114:124–129. [Europe PMC free article] [Abstract] [Google Scholar]
  • Weissman AD, Caldecott-Hazard S. In utero methamphetamine effects: I. Behavior and monoamine uptake sites in adult offspring. Synapse. 1993;13:241–250. [Abstract] [Google Scholar]
  • Whitaker-Azmitia PM. Serotonin and brain development: role in human developmental diseases. Brain Res Bull. 2001;56:479–485. [Abstract] [Google Scholar]
  • White KJ, Walline CC, Barker EL. Serotonin transporters: implications for antidepressant drug development. Aaps J. 2005;7:E421–433. [Europe PMC free article] [Abstract] [Google Scholar]
  • Williams MT, Morford LL, Wood SL, Rock SL, McCrea AE, Fukumura M, Wallace TL, Broening HW, Moran MS, Vorhees CV. Developmental 3,4-methylenedioxymethamphetamine (MDMA) impairs sequential and spatial but not cued learning independent of growth, litter effects or injection stress. Brain Res. 2003;968:89–101. [Abstract] [Google Scholar]
  • Williams MT, Schaefer TL, Ehrman LA, Able JA, Gudelsky GA, Sah R, Vorhees CV. 3,4-Methylenedioxymethamphetamine administration on postnatal day 11 in rats increases pituitary-adrenal output and reduces striatal and hippocampal serotonin without altering SERT activity. Brain Res. 2005;1039:97–107. [Europe PMC free article] [Abstract] [Google Scholar]
  • Won L, Bubula N, Heller A. Fetal exposure to (+/−)-methylenedioxymethamphetamine in utero enhances the development and metabolism of serotonergic neurons in three-dimensional reaggregate tissue culture. Brain Res Dev Brain Res. 2002;137:67–73. [Abstract] [Google Scholar]
  • Yue Y, Widmer DA, Halladay AK, Cerretti DP, Wagner GC, Dreyer JL, Zhou R. Specification of distinct dopaminergic neural pathways: roles of the Eph family receptor EphB1 and ligand ephrin-B2. J Neurosci. 1999;19:2090–2101. [Abstract] [Google Scholar]
  • Zerrate MC, Pletnikov M, Connors SL, Vargas DL, Seidler FJ, Zimmerman AW, Slotkin TA, Pardo CA. Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism. J Pharmacol Exp Ther. 2007;322:16–22. [Abstract] [Google Scholar]
  • Zhang L, Bai J, Undie AS, Bergson C, Lidow MS. D1 dopamine receptor regulation of the levels of the cell-cycle-controlling proteins, cyclin D, P27 and Raf-1, in cerebral cortical precursor cells is mediated through cAMP-independent pathways. Cereb Cortex. 2005;15:74–84. [Abstract] [Google Scholar]

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