The behavioral pharmacology of buprenorphine, a new mixed opiate agonist-antagonist and potential pharmacotherapy for heroin addiction, will be studied in a primate drug self-administration model. This research is designed to evaluate buprenorphine's reinforcing efficacy (or potential abuse liability) relative to methadone and heroi. The sensitivity and concordance of two established operant techniques for evaluating reinforcing efficacy, progressive ratio and discrete trial choice procedures, will be compared. The contribution of the antagonist component of buprenorphine to its reinforcing effects will also be examined. Two projects are concerned with the effects of abused substances on female reproductive function. The acute and chronic effects of marihuana on reproductive hormones in women will be examined in clinical studies. The acute and chronic effects of alcohol on reproductive hormones will be studied in female rhesus monkeys, trained to self-administer alcohol using established operant procedures. Marihuana and alcohol effects will be evaluated at ovulation, the mid-luteal phase, the premenstruum and menstruation. Episodic secretory profiles of pituitary (LH, FSH) and ovarian (estradiol, progesterone) hormones will be studied with integrated plasma sampling techniques and radioimmunoassay procedures. These studies are also designed to examine the covariance between marihuana or alcohol self-administration and specific phases of the menstrual cycle. The overall objectives of the proposed research are to improve understanding of the way in which drugs act as reinforcers, leading to their self-administration. A second goal is to clarify the behavioral and hormonal consequences of substance abuse. Professional growth plans include further study in the areas of reproductive physiology, neuroendocrinology and computer sciences.
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