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

The effects of in utero cocaine exposure on cocaine-induced genomic and fun ctional responses in postnatal life were examined. Pregnant Dutch Belted ra bbits were injected intravenously, twice daily, with cocaine hydrochloride (4 mg/kg) or saline from day 8 through day 29 of pregnancy. Prenatally expo sed kits were challenged with cocaine on postnatal day 20. In prenatal sali ne-exposed kits, cocaine induced time-and dose-dependent c-fos gene express ion 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 bo bbing, seizure, and locomotor activity were also attenuated in prenatal coc aine-exposed kits. Cocaine-induced c-fos expression and functional response s were blocked by the D-1 dopamine receptor antagonist, SCH23390, or by the serotonin receptor antagonist, methysergide, but not by the D-2 dopamine r eceptor antagonist, L-sulpride. The results indicate that in utero cocaine exposure leads to diminished responses to cocaine challenge in the offsprin g, which may be mediated by prenatal cocaine-induced alterations in one or more components of the D-1 dopamine and/or serotonin receptor signaling sys tems during early postnatal life. (C) 2001 Elsevier Science Inc. All rights reserved.