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

N. Tilakaratne, G. Cai, E. Friedman

Research output: Contribution to journalArticlepeer-review

Abstract

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 D1 dopamine receptor antagonist, SCH23390, or by the serotonin receptor antagonist, methysergide, but not by the D2 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 D1 dopamine and/or serotonin receptor signaling systems during early postnatal life.

Original languageEnglish
Pages (from-to)225-232
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume69
Issue number1-2
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Brain
  • c-fos
  • Functional response
  • Prenatal cocaine
  • Rabbit

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