Effects of luteinizing hormone-releasing hormone on plasma cocaine levels in rhesus monkeys

No effective pharmacotherapy for the treatment of cocaine abuse is currentl y available. In addition to pharmacological approaches, immunologic methods that use specific antibodies to bind cocaine in blood and prevent it from reaching the central nervous system are also being evaluated. There is cons iderable evidence that cocaine binds to the dopamine transporter, and there are structural similarities between the dopamine transporter and an anteri or pituitary hormone, luteinizing hormone (LH). These structural similariti es led us to hypothesize that LH may bind cocaine and decrease plasma level s of free cocaine, Synthetic LH-releasing hormone (LHRH) was used to stimul ate LH release from pituitary gonadotropes before i.v. cocaine administrati on to male and female rhesus monkeys. The effects of placebo-LHRH and 15 an d 30 mu g/kg LHRH on levels of free cocaine in plasma after i.v. administra tion of 0.8 mg/kg cocaine were studied. LHRH (15 and 30 mu g/kg) significan tly increased LH secretion in both males (P < .01-.001) and females (P < .0 1-.05). Peak plasma cocaine levels were significantly lower after both dose s of LHRH than after placebo-LHRH in males and in females (P < .05), There was an inverse relationship between peak plasma cocaine levels and LHRH-sti mulated LH levels in males (P < .01) but not in females, Pharmacokinetic an alyses showed that the time to reach peak plasma cocaine levels, the elimin ation half-life, and the area under the plasma cocaine curve did not differ as a function of the LHRH dose compared with placebo LHRH. Moreover, there were no gender differences in any cocaine-related, pharmacokinetic paramet er after placebo-LHRH administration. These data suggest the feasibility of reducing peak levels of free cocaine in plasma by stimulating secretion of LH. The functional consequences and underlying mechanisms of LHRH-induced decreases in peak plasma cocaine levels remain to be determined.