Sobrian S K, Ali S F, Slikker W, Holson R R
Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA.
Mol Neurobiol. 1995 Aug-Dec;11(1-3):121-43. doi: 10.1007/BF02740690.
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 parameters and/or fetal viability. Exposure of Sprague-Dawley rats to combined 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 that that of exposure to C alone. Experiment II investigated pregnancy outcome, postnatal development, and behavior of the offspring following drug exposure to either 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 saline-fitted 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. However, the development of surface righting was delayed inC CS pups, and only CS offspring were underresponsive to the stimulatory effects of dopamine agonists on activity and stereotypy. Behavioral responses to N challenge were similar in all groups. In addition, only CS offspring showed altered behavioral responses in a spontaneous alternation task. Treatment effects on dopamine D1 and D2 binding in the caudate nucleus were not observed. The combination of N and C did not exacerbate any of the behavioral changes seen in CS offspring. These results support the hypothesis that C is a behavioral teratogen in rodents, and suggest that in the present model, nicotine can mitigate some of the consequences of in utero exposure to cocaine.
进行了两项实验以研究产前联合给予盐酸可卡因（C）和酒石酸尼古丁（N）的交互作用。实验I旨在确定可以联合给予而不改变母体妊娠参数和/或胎儿活力的C和N的剂量。在妊娠第8 - 21天，将斯普拉格-道利大鼠暴露于高剂量C（20 mg/kg）和高剂量N（5.0 mg/kg）的联合环境中，对母鼠或胎儿的毒性并不比单独暴露于C更大。实验II研究了在妊娠第8 - 21天暴露于高剂量可卡因（20 mg/kg：CS）、高剂量尼古丁（5.0 mg/kg：NS）或两者（NC）后，后代的妊娠结局、产后发育和行为。N通过渗透微型泵给药，C通过皮下注射给药。注射生理盐水的母鼠，配备注射生理盐水的泵（SS），以及与NC组母鼠配对饲养（PF）的未处理母鼠作为对照。母体变量的改变仅限于NC和CS组食物摄入量减少10 - 15%。妊娠结局和出生统计数据不受产前治疗的影响，产后前四周的后代体重也是如此。然而，CS组幼崽的表面翻正反射发育延迟，并且只有CS组后代对多巴胺激动剂对活动和刻板行为的刺激作用反应迟钝。所有组对N激发的行为反应相似。此外，只有CS组后代在自发交替任务中表现出行为反应改变。未观察到对尾状核中多巴胺D1和D2结合的治疗效果。N和C的联合并没有加剧CS组后代中出现的任何行为变化。这些结果支持了C是啮齿动物行为致畸剂的假设，并表明在当前模型中，尼古丁可以减轻子宫内暴露于可卡因的一些后果。
