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

说明(申请人提供)：吸毒人群存在性别差异。此外，已有研究表明，女性性腺激素--雌激素和孕激素--以不同的、有时是相反的方式调节可卡因引起的行为。这项拟议的研究的主要目的是检查黄体酮对大鼠寻找可卡因行为的抑制作用。在这项拟议的研究中，将在成瘾过程的升级和维持阶段检查黄体酮作为治疗方法的有效性。将使用自治范例来评估这些影响。以下是与拟议的3个自我给药实验相对应的具体目标：目的1-检查孕酮治疗对雄性和雌性大鼠在递增比率时间表下的反应的影响，以及在由于扩大接触而导致的药物摄入量增加期间的影响。黄体酮治疗对非药物增强剂的影响也将被检测，以评估黄体酮的治疗特异性。目的2-评估黄体酮在不同可卡因寻找行为易感性人群中的治疗效果。这些种群包括：雄性与雌性，高与低冲动，以及高与低糖精偏爱大鼠。目的3-研究孕酮的一种行为活性代谢物--别孕酮在可卡因摄入量增加期间的作用。这项拟议的研究还将评估黄体酮和别孕酮作为可卡因滥用的潜在治疗方法在更多和更不脆弱的表型中的有效性。

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.