Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, 309 East 2nd Street, Pomona, CA 91766, United States.
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, 309 East 2nd Street, Pomona, CA 91766, United States.
Pharmacol Biochem Behav. 2017 Aug;159:84-89. doi: 10.1016/j.pbb.2017.07.010. Epub 2017 Jul 20.
Previous preclinical studies have shown that nicotine pretreatment during adolescence increases the reinforcing actions of cocaine. However, little is known about the effect of prior nicotine administration on cocaine-induced conditioned place preference (CPP) and its reinstatement in adult mice. Besides, little information is available regarding the role of sex in this cross-talk between nicotine and cocaine. Thus, we examined if nicotine administration during adulthood would differentially alter cocaine-induced CPP, its extinction and reinstatement in male versus female mice and if the dose of nicotine was important in this regard. To this end, mice were pretreated with saline or nicotine (0.25 or 1mg/kg; twice daily for seven days) and then tested for place preference before and after single and repeated conditioning with cocaine (15mg/kg). Mice were then exposed to extinction training and tested for reinstatement of CPP. Our results showed that male and female mice pretreated with saline and conditioned with cocaine each exhibited a robust CPP after a single cocaine conditioning. However, this response was blunted in mice pretreated with the lower but not higher dose of nicotine. Female mice pretreated with the lower dose nicotine also failed to show CPP after repeated conditioning. Reinstatement of cocaine-induced CPP was also blunted in these mice compared to their respective controls. Together, these results suggest that nicotine administration during adulthood exerts differential effects on cocaine-induced CPP and its reinstatement in male and female mice and the dose of nicotine is important in this regard.
先前的临床前研究表明，青春期时的尼古丁预处理会增加可卡因的强化作用。然而，对于先前给予尼古丁对成年小鼠可卡因诱导的条件位置偏好（CPP）及其复燃的影响知之甚少。此外，关于尼古丁和可卡因之间这种相互作用中性别所起的作用，相关信息也很少。因此，我们研究了成年期给予尼古丁是否会以不同的方式改变雄性和雌性小鼠中可卡因诱导的 CPP 及其消退和复燃，如果在这方面尼古丁的剂量很重要。为此，我们用生理盐水或尼古丁（0.25 或 1mg/kg；每天两次，持续七天）预处理小鼠，然后在单次和重复给予可卡因（15mg/kg）之前和之后测试它们的位置偏好。然后，将小鼠暴露于消退训练中，并测试 CPP 的复燃情况。我们的结果表明，用生理盐水预处理并用可卡因条件化的雄性和雌性小鼠在单次可卡因条件化后都表现出强烈的 CPP。然而，在接受较低但不是较高剂量尼古丁预处理的小鼠中，这种反应减弱了。用较低剂量尼古丁预处理的雌性小鼠在重复条件化后也未能表现出 CPP。与各自的对照组相比，这些小鼠的可卡因诱导的 CPP 复燃也减弱了。这些结果表明，成年期给予尼古丁会对雄性和雌性小鼠中可卡因诱导的 CPP 及其复燃产生不同的影响，而且尼古丁的剂量在这方面很重要。
