The effect of N-nitro-L-arginine methyl ester on cocaine-induced hormonal changes in mice.

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Effects of the nitric oxide synthase inhibitor, N-nitroL-arginine methyl ester (L-NAME, 30 mg/kg i.p.), on cocaine-induced changes in corticosterone and testosterone plasma levels were studied in male mice. Acute (30 mg/kg i.p.) and repeated cocaine (30 mg/kg i.p., twice a day for four days) enhanced the corticosterone level after 45 min and 2 hr, respectively. Single administration of L-NAME had no effect on corticosterone level, whereas its repeated injections (30 mg/kg i.p., twice a day for four days) elevated the hormone concentration at 2 hr after the last dose. Pretreatment of mice with L-NAME enhanced the stimulatory effects of both acute and repeated cocaine on corticosterone level. D-NAME (30 mg/kg i.p.), an inactive form of the nitric oxide synthase inhibitor, was without effect on the cocaine-induced changes in corticosterone level. Acute cocaine administration (30 mg/kg) moderately decreased the testosterone plasma level after 45 min and 2 hr; however, that effect disappeared upon repeated cocaine administration. Single and repeated L-NAME administration did not influence the testosterone level in control animals. Single L-NAME injection abolished the decrease in testosterone level evoked by acute cocaine administration. The above results show that inhibition of nitric oxide synthase enhances the stimulatory effect of cocaine on corticosterone secretion, but abolishes the inhibitory effect of this psychostimulant on the plasma testosterone concentration in mice. On the other hand, a weak--if any--effect of L-NAME alone on corticosterone and testosterone levels suggests that nitric oxide plays a minor role in the tonic regulation of these hormones' secretion.