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

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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.