Effects of prenatal cocaine exposure upon postnatal development of neostriatal dopaminergic function

Leslie, Catherine Amoroso; Robertson, Matthew; Jung, Anthony B.; Liebermann, Jennifer; Bennett, James P.

doi:10.1002/syn.890170311

Cited by 57 publications

(45 citation statements)

References 33 publications

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“…In contrast with the effects of dopamine receptor antagonists, the behavioral changes observed in rodents after prenatal exposure to cocaine described previously were not associated with consistent or persistent changes in the density or in the affinity of dopamine receptors (Mayfield et al, 1992;Leslie et al, 1994;Scalzo et al, 1990). Thus, prenatal cocaine exposure resulted in increases in striatal D 2 receptor ligand binding at postnatal days 6-35 (Leslie et al, 1994) due to an increased D2 ligand affinity (Scalzo et al, 1990), and exhibited a corresponding increased sensitivity to the D2 agonist quinpirole (Moody et al, 1992). However, these changes did not appear to extend into adulthood.…”

Section: Introductioncontrasting

confidence: 49%

“…Furthermore, prenatal exposure of rodents to dopamine receptor inhibition affects maze learning and motor activity levels (Clark et al, 1970) as well as sensitivity to dopamine antagonists when exposed offspring were tested as adults (Golub and Kornetsky, 1975). In contrast with the effects of dopamine receptor antagonists, the behavioral changes observed in rodents after prenatal exposure to cocaine described previously were not associated with consistent or persistent changes in the density or in the affinity of dopamine receptors (Mayfield et al, 1992;Leslie et al, 1994;Scalzo et al, 1990). Thus, prenatal cocaine exposure resulted in increases in striatal D 2 receptor ligand binding at postnatal days 6-35 (Leslie et al, 1994) due to an increased D2 ligand affinity (Scalzo et al, 1990), and exhibited a corresponding increased sensitivity to the D2 agonist quinpirole (Moody et al, 1992).…”

Section: Introductionmentioning

confidence: 90%

“…Previous studies in the rodent have reported that prenatal exposure to cocaine can produce a number of presynaptic effects on dopaminergic neurons such as decrease in the number of dopamine neurons in the midbrain A9 and A10 cell groups (Minabe et aI., 1992;Wang and Pitts, 1994) and alterations in the striatal dopamine transporter (Leslie et al, 1994). Prenatal cocaine exposure in the rat has been also reported to produce an increase in basal levels of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) as measured by microdialysis at postnatal days 10-30 as well as a greater increase in extracellular dopamine in response to tail pinch or cocaine injection (Keller et al, 1994).…”

Section: Introductionmentioning

confidence: 98%

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Effects of prenatal exposure to cocaine on the developing brain: Anatomical, chemical, physiological and behavioral consequences

et al. 2001

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Earlier studies of human infants and studies employing animal models had indicated that prenatal exposure to cocaine produced developmental changes in the behavior of the offspring. The present paper reports on the results obtained in a rabbit model of in utero exposure to cocaine using intravenous injections (4 mg/kg, twice daily) that mimic the pharmacokinetics of crack cocaine in humans. At this dose, cocaine had no effect on the body weight gain of dams, time to delivery, litter size and body weight or other physical characteristics of the offspring. In spite of an otherwise normal appearance, cocaine-exposed neonates displayed a permanent impairment in signal transduction via the D1 dopamine receptor in caudate nucleus, frontal cortex and cingulate cortex due to an uncoupling of the receptor from its associated Gs protein. This uncoupling in the caudate nucleus was shown to have behavioral consequences in that young or adult rabbits, exposed to cocaine in utero, failed to demonstrate amphetamine-elicited motor responses normally seen after activation of D1 receptors in the caudate. The cocaine progeny also demonstrated permanent morphological abnormalities in the anterior cingulate cortex due to uncoupling of the D1 receptor and the consequent inability of dopamine to regulate neurite outgrowth during neuronal development. Consistent with the known functions of the anterior cingulate cortex, adult cocaine progeny demonstrated deficits in attentional processes. This was reflected by impairment in discrimination learning during classical conditioning that was due to an inability to ignore salient stimuli even when these were not relevant to the task. The impairment in discrimination learning also occurred in an instrumental avoidance task and could be shown to be due to an impairment of cingulothalamic learning-related neuronal coding. It was proposed that the selective loss of D1-related neurotransmission in the anterior cingulate cortex prevented an appropriate activation of GABA neurons and thus a loss of inhibitory regulation that is necessary for processes involved in associative attention. Taken together, these findings suggest that the uncoupling of the D1 receptor from its G protein may be the fundamental source of the anatomic, cognitive and motor disturbances seen in rabbits exposed to cocaine in utero. Moreover, the long-term cognitive and motor deficits observed in the rabbit model are in agreement with the recent reports indicating that persistent attentional and other behavioral deficits may be evident in cocaine-exposed children as they grow older and are challenged to master more complex cognitive tasks.

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Section: Introductioncontrasting

confidence: 49%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 98%

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Effects of prenatal exposure to cocaine on the developing brain: Anatomical, chemical, physiological and behavioral consequences

et al. 2001

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“…However, this mechanism is unlikely on the basis of previous findings that prenatal exposure to cocaine (1) did not affect D 1 mRNAs (DeBartolomeis et al, 1994) or receptor binding in the striatum, nucleus accumbens, or ventral tegmental area (Leslie et al, 1994) and (2) resulted in decreased D 1 receptor G-protein coupling in the striatum, anterior cingulate, and frontal cortex (Wang et al, 1995b;Friedman et al, 1996;Levitt et al, 1997). In fact, this latter finding of reduced D 1 coupling in intravenous cocaine-exposed rabbits appears inconsistent with the present findings.…”

Section: Discussionmentioning

confidence: 90%

Prenatal Cocaine Exposure Increases Sensitivity to the Attentional Effects of the Dopamine D1 Agonist SKF81297

Bayer¹,

Brown²,

Mactutus³

et al. 2000

J. Neurosci.

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Sensitivity to the attentional effects of SKF81297, a selective full agonist at dopamine D 1 receptors, was assessed in adult rats exposed to cocaine prenatally (via intravenous injections) and controls. The task assessed the ability of the subjects to monitor an unpredictable light cue of either 300 or 700 msec duration and to maintain performance when presented with olfactory distractors. SKF81297 decreased nose pokes before cue presentation and increased latencies and response biases (the tendency to respond to the same port used on the previous trial), suggesting an effect of SKF81297 on the dopamine (DA) systems responsible for response initiation and selection. The cocaine-exposed (COC) and control animals did not differ in sensitivity to the effects of SKF81297 on these measures. In contrast, the COC animals were significantly more sensitive than were controls to the impairing effect of SKF81297 on omission errors, a measure of sustained attention. This pattern of results provides evidence that prenatal cocaine exposure produces lasting changes in the DA system(s) subserving sustained attention but does not alter the DA system(s) underlying response selection and initiation. These findings also provide support for the role of D 1 receptor activation in attentional functioning.Key words: prenatal cocaine; intravenous injection; catecholamine; dopamine; attention; response initiation; response selection Concern about effects of prenatal cocaine exposure has grown in recent years. Although early media reports of gross neurological sequelae have proven primarily unfounded, recent controlled studies have revealed attentional dysfunction in exposed children that persists into school-age years (Richardson et al., 1996;Mayes et al., 1998;Dow-Edwards et al., 1999;Leech et al., 1999). Because maternal cocaine use in these studies generally occurred within the context of multiple risk factors, including polydrug abuse, it is important that animal model studies have demonstrated a clear causal link between prenatal cocaine exposure and attentional dysfunction (Romano and Harvey, 1996;Morgan et al., 1997; Wilkins et al., 1998a,b;Mactutus, 1999;Garavan et al., 2000). Elucidation of the neural bases of these deficits might allow amelioration or reversal of the dysfunction. This goal motivated the present study.Altered dopamine (DA) activity, particularly in prefrontal and anterior cingulate cortices, is one mechanism that may underlie prenatal cocaine-induced attentional deficits. Moderate DA activity is critical for the optimal functioning of frontal cortical regions (for review, see Robbins et al., 1994;Arnsten, 1997), thought to subserve attentional functions impaired by cocaine exposure (for review, see Arnsten et al., 1994;Arnsten, 1997;Carter et al., 1997;Coull, 1998;Posner and Rothbart, 1998;Garavan et al., 2000). Prenatal cocaine exposure has been reported to disrupt CNS DA function (for review, see Mayes, 1999). However, definitive conclusions about the role of DA alterations in prenatal cocaineinduced attenti...

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“…However, the results are inconsistent: one study states that adult mice with prenatal cocaine exposure (GD 13-21) showed a reduction of DAT in the striatum [44], whereas other reports suggest that prenatal cocaine exposure (GD 18-21) resulted in a transient decrease in DA transporter binding in the dorsal lateral striatum at PD10 [45], with no change at adult age. Leslie et al [47] found that prenatal cocaine exposure (GD10-21) caused an increase in DAT density from PD1 to PD5; however after PD14 they observed a reduction in DAT. Different prenatal periods of exposure and doses may explain these differences.…”

Section: Discussionmentioning

confidence: 95%

Prenatal Amphetamine Exposure Effects on Dopaminergic Receptors and Transporter in Postnatal Rats

2011

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We investigated the influence of prenatal amphetamine exposure (PAE) on dopamine (DA) receptors, and dopamine transporter (DAT) in various striatal and limbic subregions and locomotor activity induced by novel environmental conditions and amphetamine at two postnatal ages, 35 days old (prepubertal) and 60 days old (postpubertal). Experiments were carried out on pregnant female Sprague-Dawley rats, which were daily injected with either d-amphetamine sulfate (1 mg/kg) or saline solution (0.9%) for 11 days, from gestation day 11-21. In PAE rats compared to control we found the following: at pre-pubertal age, an enhancement of DA D1 in the dorsolateral area of the caudate-putamen (CPu), CPu-ventral and shell of the nucleus accumbens (NAcc) with a decrement of the DA D3 receptors in NAcc, olfactory tubercle (OT), and the islands of Calleja (IoC); whereas at postpubertal age, an increase in the levels of DAT in the NAcc and fundus of the CPu, and OT along with a decrease in the expression of DA D2 receptors only in the NAcc shell were found in PAE rats compared to control. In addition, amphetamine induces a marked decrease in locomotor activity at postpubertal age in rats with PAE. These results suggest a differential effect of amphetamines on the DAT mechanism of the nervous system during embryonic development of animals with implications in behavior and drug addictions at adulthood age.

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Effects of prenatal cocaine exposure upon postnatal development of neostriatal dopaminergic function

Cited by 57 publications

References 33 publications

Effects of prenatal exposure to cocaine on the developing brain: Anatomical, chemical, physiological and behavioral consequences

Effects of prenatal exposure to cocaine on the developing brain: Anatomical, chemical, physiological and behavioral consequences

Prenatal Cocaine Exposure Increases Sensitivity to the Attentional Effects of the Dopamine D1 Agonist SKF81297

Prenatal Amphetamine Exposure Effects on Dopaminergic Receptors and Transporter in Postnatal Rats

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