INTERACTIVE EFFECTS OF PRENATAL COCAINE AND NICOTINE EXPOSURE ON MATERNAL TOXICITY, POSTNATAL-DEVELOPMENT, AND BEHAVIOR IN THE RAT

Two experiments were performed to investigate the interactive effects of prenatal coadministration of cocaine hydrochloride (C) and nicotine tartrate (N). Experiment I was designed to determine doses of C and N that could be coadministered without altering maternal gestational pa rameters and/or fetal viability. Exposure of Sprague-Dawley rats to co mbined high-dose C (20 mg/kg) and high-dose N (5.0 mg/kg) on gestation days 8-21 was not more toxic to dam or fetus than that of exposure to C alone. Experiment II investigated pregnancy outcome, postnatal deve lopment, and behavior of the offspring following drug exposure to eith er high-dose cocaine (20 mg/kg: CS), high-dose nicotine (5.0 mg/kg: NS ), or both (NC) on gestation days 8-21. N was administered by osmotic minipump and C by sc injection. Saline-injected dams, fitted with sali ne-filled pumps (SS), and untreated dams, pair-fed (PF) to NC females, served as controls. Alterations in maternal variables were limited to a 10-15% decrease in food consumption in NC and CS groups. Pregnancy outcome and birth statistics were unaffected by prenatal treatment, as was offspring body weight during the first four postnatal weeks. Howe ver, the development of surface righting was delayed in CS pups, and o nly CS offspring were underresponsive to the stimulatory effects of do pamine agonists on activity and stereotypy. Behavioral responses to N challenge were similar in all groups. In addition, only CS offspring s howed altered behavioral responses in a spontaneous alternation task. Treatment effects on dopamine D-1 and D-2 binding in the caudate nucle us were not observed. The combination of N and C did not exacerbate an y of the behavioral changes seen in CS offspring. These results suppor t the hypothesis that C is a behavioral teratogen in rodents, and sugg est that in the present model, nicotine can mitigate some of the conse quences of in utero exposure to cocaine.