Cocaine Effects on Luteinizing Hormone-Releasing Hormone-Stimulated Anterior Pituitary Hormones in Female Rhesus Monkey*

Abstract
The effects of acute cocaine administration on synthetic LHRH-stimulated anterior pituitary hormones (LH, FSH, and PRL) were studied in 6 female rhesus monkeys during the follicular phase of the menstrual cycle (days 4-7). Integrated plasma samples were collected every 10 min for 40 min before iv administration of cocaine (0.4 or 0.8 mg/kg) or an equal volume of vehicle control solution. Synthetic LHRH (100 .mu.g, iv) was administered 10 min after cocaine or placebo-cocaine administration, and 10 plasma samples were collected for an additional 100 min. LHRH stimulated a significant increase in LH within 10 min after placebo-cocaine administration (P < 0.05) and after each dose of cocaine (P < 0.0001). Cocaine (0.4 mg/kg) significantly enhanced LHRH-stimulation of LH compared to placebo or 0.8 mg/kg cocaine administration (P < 0.01). FHS increased signficantly within 20-30 min after LHRH alone (P < 0.008) and after 0.4 mg/kg cocaine (P < 0.0001). LHRH-stimulated FSH levels also were significantly higher after 0.4 mg/kg cocaine than after placebo or 0.8 mg/kg cocaine (P < 0.01). These data indicate that cocaine does not suppress LHRH stimulation of pituitary gonadotropins, and low doses of cocaine significantly enhance LH and FSH release. Consequently, cocaine does not compromise anterior-pituitary function at the level of the gonadotroph and may stimulate hypothalamic release of endogenous LHRH. PRL levels were unchanged by LHRH and placebo-cocaine administration. After LHRH and cocaine administration, PRL levels decreased significantly (P < 0.05-0.01) and remained suppressed throughout the 110-min postcocaine sampling period. These data indicate that cocaine''s significant suppression of PRL is not blocked by LHRH. These findings are consistent with dopaminergic inhibitory control of PRL and suggest that cocaine''s inhibition of dopamine reuptake down-regulates pituitary lactotroph activity in rhesus monkey.