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Attenuation of cocaine-induced genomic and functional responses in prenatal cocaine-exposed rabbits
Journal article   Peer reviewed

Attenuation of cocaine-induced genomic and functional responses in prenatal cocaine-exposed rabbits

N Tilakaratne, G Cai and E Friedman
Pharmacology, biochemistry and behavior, v 69(1-2), pp 225-232
May 2001
PMID: 11420090

Abstract

Animals Behavior, Animal - drug effects Brain Chemistry - drug effects Cocaine - administration & dosage Cocaine - pharmacology Dopamine Antagonists - pharmacology Dopamine Uptake Inhibitors - administration & dosage Dopamine Uptake Inhibitors - pharmacology Dose-Response Relationship, Drug Female Gene Expression Regulation - drug effects Genes, fos - drug effects Motor Activity - drug effects Prenatal Exposure Delayed Effects Rabbits RNA - biosynthesis RNA - isolation & purification Seizures - chemically induced Serotonin Antagonists - pharmacology Pregnancy
The effects of in utero cocaine exposure on cocaine-induced genomic and functional responses in postnatal life were examined. Pregnant Dutch Belted rabbits were injected intravenously, twice daily, with cocaine hydrochloride (4 mg/kg) or saline from day 8 through day 29 of pregnancy. Prenatally exposed kits were challenged with cocaine on postnatal day 20. In prenatal saline-exposed kits, cocaine induced time- and dose-dependent c-fos gene expression in both frontal cortex and striatum. Prenatal cocaine exposure reduced cocaine-induced c-fos responses by 35-58% in the frontal cortex and 37-41% in the striatum. Cocaine-induced functional responses that included head bobbing, seizure, and locomotor activity were also attenuated in prenatal cocaine-exposed kits. Cocaine-induced c-fos expression and functional responses were blocked by the D(1) dopamine receptor antagonist, SCH23390, or by the serotonin receptor antagonist, methysergide, but not by the D(2) dopamine receptor antagonist, L-sulpride. The results indicate that in utero cocaine exposure leads to diminished responses to cocaine challenge in the offspring, which may be mediated by prenatal cocaine-induced alterations in one or more components of the D(1) dopamine and/or serotonin receptor signaling systems during early postnatal life.

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Web of Science research areas
Behavioral Sciences
Neurosciences
Pharmacology & Pharmacy
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