PRENATAL COCAINE AND OR NICOTINE EXPOSURE IN RATS - PRELIMINARY FINDINGS ON LONG-TERM COGNITIVE OUTCOME AND GENITAL DEVELOPMENT AT BIRTH/

Prenatal cocaine or nicotine exposure is associated with a variety of teratogenic effects. The current study was conducted to determine thei r effects alone and in combination on cognitive function and sexual di fferentiation. Pregnant Long-Evans rats (N = 19) were exposed to eithe r cocaine (15 mg/kg/dose b.i.d. SC on GD 8-20); nicotine (4 mg/kg/day continuous SC infusion on GD 4-20); both nicotine + cocaine; or vehicl e only. Birth weight and anogenital distance (AGD) were measured in al l pups at birth. Learning and memory were tested in the Morris water m aze (MWM) during prepubertal and pubertal ages in five daily consecuti ve sessions and a sixth session 1 week later and in the radial-arm maz e (RAM) during adulthood. In the RAM, a drug challenge of the beta-nor adrenergic antagonist propranolol (10-20 mg/kg) was given after acquis ition training. Maternal weight gain was reduced 13-42% and offspring birth weight was reduced by 7-12% in all three exposure groups compare d to controls. Cocaine decreased the AGD of males (2.68 mm) compared t o 2.88 mm in noncocaine-exposed male pups (p < 0.025). A sex-selective cocaine effect was also seen after adjustment of AGD measurements for body weight. With this measure cocaine-treated females showed signifi cantly (p < 0.05) greater AGD than those not exposed to cocaine. In th e MWM, there were two types of trials: cued reference memory trials an d uncued spatial working memory trials. On cued reference memory trial s significant cocaine-induced latency deficits were seen on only the f irst session. On spatial working memory trials cocaine-induced latency deficits were seen throughout daily training on sessions 1-5, but not the retention session 6, 1. week later. During RAM acquisition, there were no significant differences in choice accuracy between exposure g roups. Following propranolol challenge, deficits in choice accuracy we re demonstrated in rats prenatally exposed to cocaine or nicotine. The se rats did not show any response to propranolol, whereas the controls slightly improved their choice accuracy. The results of this study in dicated that prenatal cocaine exposure altered long-term cognitive fun ction under basal conditions in the MWM and drug challenge in the RAM, birth weight, and genital development. Cocaine-induced cognitive defi cits were predominately in working memory rather than reference memory or long-term retention. Prenatal nicotine exposure was only observed to alter birth weight and cognitive function in response to propranolo l challenge in the RAM. Copyright (C) 1996 Elsevier Science Inc.