Precoital single doses of delta9-tetrahydrocannabinol block ovulation in the rabbit.
delta9-Tetrahydrocannabinol (delta9-THC) inhibits pituitary gonadotropin secretion in castrated rhesus monkeys. Also, delta9-THC blocks the ovulatory reflux in rabbits. We report now the dose-response relationship of precoital single doses of delta9-THC on luteinizing hormone (LH) release and ovulation in the rabbit. Forty-five female rabbits in estrous were divided into nine groups of five animals. Groups 1 to 5 received a single intramuscular dose of delta9-THC (5,2.5, 1.25, 0.612, and 0.306 mg/kg, respectively) 2 hours before mating; animals of group 6 received vehicle only. In animals of groups 7 and 8 ovulation was induced with 100 IU of human chorionic gonadotropic (hCG), given intravenously 2 hours after the administration of delta9-THC (5 mg/kg) or vehicle. Rabbit luteinizing hormone (rLH) was measured in plasma 90 to 120 minutes after coitus or hCG administration. After the injection of 5 mg of delta9-THC, luteinizing hormone-releasing factor (LH-RF) (20 microgram intravenously) was administered to the animals of group 9. All animals of groups 6, 7, and 8 ovulated. A dose-response curve was observed in the animals treated with delta9-THC and natural mating. Whereas none of the animals treated with 5 or 2.5 mg/kg ovulated, one of the group treated with 1.25 mg/kg, two of the group treated with 0.612 mg/kg, and all treated with 0.312 mg/kg ovulated. Ovulations correlated with postcoital levels of rLH. All animals of group 9 ovulated, indicating that the site of action of delta9-THC is suprapituitary, probably hypothalamic.
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003307:Copulation; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects; D007273:Injections, Intramuscular; D007986:Luteinizing Hormone / Q000097:blood; D010060:Ovulation / Q000187:drug effects*; D011817:Rabbits
D006063:Chorionic Gonadotropin; D007987:Gonadotropin-Releasing Hormone; D013759:Dronabinol; D007986:Luteinizing Hormone