Progesterone as a Treatment for Cocaine Abuse in Rats with Differing Vulnerabilit

描述（申请人提供）：药物滥用人群存在性别差异。此外，研究表明，雌性性腺激素雌激素和孕激素以不同的方式调节可卡因引起的行为，有时甚至是相反的方式。这项研究的主要目的是检查孕酮对大鼠可卡因寻求行为抑制的影响。在拟议的研究中，孕酮作为一种治疗方法的有效性将在成瘾过程的升级和维持阶段进行检查。自我管理模式将被用来评估这些影响。以下是与3项拟定的自我给药实验对应的具体目的：目的1 -检查雄性和雌性大鼠中孕酮给药对渐进比例方案下和由于延长给药时间导致药物摄入量增加期间反应的影响。还将检查孕酮治疗对非药物促孕剂的影响，以评估孕酮的治疗特异性。目的2 -评估孕酮作为治疗可卡因寻求行为的脆弱性不同的人群的治疗效果。这些种群包括：雄性与雌性、高冲动与低冲动、高糖精偏好与低糖精偏好大鼠。目的3 -检查的影响孕激素的行为活性，代谢产物，别孕烯醇酮，在可卡因摄入量的升级。拟议的研究还将评估孕酮和别孕烯醇酮作为可卡因滥用的潜在治疗方法在更多和更少脆弱表型中的有效性。

DESCRIPTION (provided by applicant): Sex differences exist in drug abusing populations. In addition, it has been shown that the female gonadal hormones, estrogen and progesterone, modulate behavior elicited by cocaine in different and sometimes opposite ways. The primary aim of the proposed research is to examine the effects of progesterone on the inhibition of cocaine-seeking behavior in rats. In the proposed research, the effectiveness of progesterone as a treatment will be examined in the escalation and maintenance phases of the addiction process. The self-administration paradigm will be used to asses these effects. The following are specific aims that correspond to the 3 proposed self-administration experiments: Aim 1 - to examine the influence of progesterone treatment in male and female rats on responding under a progressive ratio schedule and during escalation of drug intake due to extended access. The effects of progesterone treatment on nondrug reinforcers will also be examined to assess progesterone's therapeutic specificity. Aim 2 - to assess the therapeutic effectiveness of progesterone as a treatment in populations that differ in the vulnerability to cocaine-seeking behavior. These populations include: male vs. female, high vs. low impulsive, and high vs. low saccharin preferring rats. Aim 3 - to examine the effects of one of progesterone's behaviorally active, metabolites, allopregnanolone, during the escalation of cocaine intake. The proposed research will also assess the effectiveness of progesterone and allopregnanolone as potential treatments for cocaine abuse in more and less vulnerable phenotypes.