COCAINE: EFFECTS ON OVARIAN FUNCTION

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Society is experiencing an epidemic of cocaine use fueled by a vastly expanded supply and decreased price. Cocaine use has become more prevalent among women of child-bearing age and even pregnant women. Other than adverse effects on fetus and neonate, little is known about cocaine's effects on female reproductive function. The major objective of this proposal is to determine if exposure to intravenous cocaine impairs rabbit ovarian function. The specific aims are: (1) To determine if cocaine, administered to rabbits either as a single dose or as repeated daily injections, affects ovarian function. (2) If ovarian effects are observed, to determine if the rabbit ovary contains specific receptors for cocaine. (3) If ovarian receptors are identified, to determine the tissue receptor pattern for cocaine. Study 1 will assess if a single injection of cocaine will affect gonadotropin-induced ovulation, oocyte maturation, corpus luteum formation, fertilization and/or preimplantation embryonic development. Animals will be injected with an ovulation-inducing dose of human chronic gonadotropin (hCG) and treated with cocaine. Ovulated oocytes will be retrieved, examined for stage of maturity, and inseminated in vitro. Fertilization and preimplantation development will be monitored daily for 5 days, when normal embryos are expected to have reached the blastocyst stage. If no effect is found, Study 2 will examine if cocaine administered intravenously daily for 14 days before ovulation induction affects these parameters. Study 3 will determine if the adverse effects of cocaine on ovarian function observed in intact animals are due to direct effect on the ovary. Isolated rabbit ovaries will be perfused in vitro in the presence or absence of cocaine. Ovulation will be induced by addition of hCG to the perfusion medium and ovulated ova will be retrieved, inseminated, and monitored as in Study 1. Incubation of [3H] cocaine in the presence and absence of unlabeled drug in Study 4 will determine if observed ovarian effects are mediated through specific ovarian receptors. If high-affinity specific ovarian receptors are found, radioautography of ovarian tissue in incubated with [3H] cocaine (Study 5) will determine which ovarian tissue(s) bear receptors and therefore are potential targets for drug action. The proposed experiments will uncover adverse effects of cocaine on early reproductive events. By publicizing these adverse effects, it may be possible to convince women to abstain from cocaine before conception.