Acquisition and maintenance of cocaine self-administration in adolescent rats: effects of sex and gonadal hormones
Acquisition and maintenance of cocaine self-administration in adolescent rats: effects of sex and gonadal hormones
复制标题
DOI：
10.1007/s00213-007-1028-0
复制
发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Lynch, Wendy J.
中科院分区：
文献类型：
--
作者：
Lynch, Wendy J.
理论基础
先前的研究表明，成年雌性大鼠比成年雄性大鼠对可卡因的强化作用更敏感，这种效应似乎至少部分是由于卵巢激素所致。
目的
在本研究中，我们检验青春期（一个激素变化显著的时期）可卡因自我给药的性别差异。
材料与方法
从出生后第30天开始，青春期的雄性和雌性斯普拉格 - 道利大鼠在固定比率1的程序下（即每次反应都通过注射一次可卡因得到强化）被训练自行注射可卡因（每次注射0.75毫克/千克）。在习得之后，根据渐进比率程序评估反应，直至出生后第50天，在前五次实验前进行血液采样，以确定性腺激素（即雌二醇、孕酮和睾酮）与可卡因动机之间的关系。在整个研究过程中监测发情周期阶段。对不同组的青春期雄性和雌性大鼠获取蔗糖强化以及对蔗糖强化的渐进比率反应进行比较。
结果
雌性比雄性更容易习得可卡因自我给药，且习得自我给药的雌性比例更高。在渐进比率测试条件下，青春期雌性为获得可卡因注射比青春期雄性反应更强烈，并且在雌性中，反应与雌二醇水平呈正相关，在发情期反应最强。在蔗糖强化方面未观察到性别差异。
结论
这些发现表明，性别差异在青春期是相关的，有证据表明循环中的雌二醇水平是导致雌性对可卡因强化作用敏感性增强的一个因素。
Rationale Previous work has shown that adult female rats are more sensitive than adult male rats to the reinforcing effects of cocaine, an effect that appears to be due, at least in part, to ovarian hormones.Objective In this study, we examine sex differences in cocaine self-administration during adolescence, a period of marked hormonal change.Materials and methods Adolescent male and female Sprague-Dawley rats were trained to self-administer cocaine (0.75 mg/kg per infusion) under a fixed ratio 1 schedule (i.e., each response was reinforced by an infusion of cocaine) beginning on postnatal day 30. After acquisition, responding was assessed under a progressive-ratio schedule until postnatal day 50 with blood sampling occurring before the first five sessions to determine the relationship between gonadal hormones (i.e., estradiol, progesterone, and testosterone) and motivation for cocaine. Estrous cycle phase was monitored throughout the study. Separate groups of adolescent male and female rats were compared on the acquisition of and progressive-ratio responding for sucrose reinforcement.Results Females acquired cocaine self-administration more readily than did males, and a greater percentage of females acquired self-administration. Under progressive-ratio testing conditions, adolescent females responded at higher levels than adolescent males to obtain cocaine infusions, and in females, responding was positively associated with levels of estradiol and greatest during estrus. No sex differences were observed for sucrose reinforcement.Conclusion These findings suggest that sex differences are relevant during adolescence with evidence implicating circulating estradiol level as a factor that contributes to the enhanced sensitivity in females to the reinforcing effects of cocaine.