Effects of Sex and Estrogen on Drug Self-Administration

描述：（申请人提供） 这项提案旨在研究性和雌激素对 静脉内（i. v.）给老鼠注射药物四 动物模型将用于研究获得，维持， 调节/失调和恢复药物自我给药。的 性和雌激素对海洛因、甲基苯丙胺和 d，1-3，4-亚甲二氧基甲基苯丙胺（MDMA）自我给药将是 使用自动整形程序进行检查。累进比率（PR）时间表 强化和需求的行为经济分析将被用来 评估性别和雌激素对可卡因维持的影响， 海洛因自我给药根据PR计划获得的断点（BP）测量值， 沿着与斜率和从需求曲线获得的P-max值将被用于 评估几剂可卡因和海洛因的强化效果。 将使用可卡因自我给药的差异化机会来调查 性别对可卡因摄入调节/失调的影响。 将获得可卡因的剂量反应曲线以检查组间差异 剂量反应曲线的变化。雌激素对 可卡因自我给药的恢复将使用预激 药物恢复模型，其中通过以下方式消除对药物的杠杆按压 用生理盐水代替可卡因恢复响应 然后通过注射可卡因来测试。

DESCRIPTION: (provided by applicant) This proposal was designed to examine the effects of sex and estrogen on the self-administration of intravenously (i.v.) delivered drugs in rats. Four animal models will be used to investigate acquisition, maintenance, regulation/dysregulation, and reinstatement of drug self-administration. The effects of sex and estrogen on the acquisition of heroin, methamphetamine and d, 1-3, 4-methylenedioxymethamphetamine (MDMA) self-administration will be examined using an autoshaping procedure. A progressive ratio (PR) schedule of reinforcement and a behavioral economic analysis of demand will be used to evaluate the effects of sex and estrogen on the maintenance of cocaine and heroin self-administration. Breakpoint (BP) measures obtained on a PR schedule, along with slopes and P-max values obtained from demand curves will be used to evaluate the reinforcing efficacy of several doses of cocaine and heroin. Differential access to cocaine self-administration will be used to investigate the effect of sex on the regulation/dysregulation of cocaine intake. Dose-response curves for cocaine will be obtained to examine group differences in shifts in the dose-response curves. The effect of estrogen on the reinstatement of cocaine self-administration will be examined using a priming model of drug reinstatement in which lever pressing for drug is extinguished by replacing cocaine infusions with saline infusions. Reinstatement of responding is then tested by administering a priming injection of cocaine.