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

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

John Harvey, Anthony Romano, Michael Gabriel, Kenny Simansky, Wei Du, Vincent Aloyo and Eitan Friedman
Neurotoxicity research, v 3(1)
Jan 2001
DOI: https://doi.org/10.1007/BF03033234
PMID: 15111265
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Neurosciences Dopamine, D 1 Dopamine receptor Neurobiology Rabbit Neuronal coding Caudate nucleus Multi-unit neuronal activity Cingulate cortex Cingulothalamic neuronal activity Discrimination learning Dopamine transporter Pharmacology/Toxicology Neurochemistry Attentional deficits Parental cocaine Classical conditioning Dopamine receptor-G Protein coupling Neurology Biomedicine Amphetamine Microdialysis Pharmaceutical Sciences/Technology Frontal cortex Instrumental avoidance learning Cocaine Motor function
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 ofin 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 cocainein 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 cocainein utero. Moreover, the long-term cognitive and motor deficits observed in the rabbit model are in agreement with 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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23 citations in Web of Science
27 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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