THE EFFECT OF N-NITRO-L-ARGININE METHYL-ESTER ON COCAINE-INDUCED HORMONAL CHANGES IN MICE

Effects of the nitric oxide synthase inhibitor, N-nitro-L-arginine met hyl eater (L-NAME, 30 mg/kg i.p.), on cocaine-induced changes in corti costerone and testosterone plasma levels were studied in male mice. Ac ute (30 mg/kg i.p.) and repeated cocaine (30 mg/kg i.p., twice a day f or four days) enhanced the corticosterone level after 45 min and 2 hr, respectively. Single administration of L-NAME had no effect on cortic osterone 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 stimulato ry 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 corti costerone level. Acute cocaine administration (30 mg/kg) moderately de creased the testosterone plasma level after 45 min and 2 hr; however, that effect dissappeared 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 decrea se in testosterone level evoked by acute cocaine administration. The a bove results show that inhibition of nitric oxide synthase enhances th e stimulatory effect of cocaine on corticosterone secretion, but aboli shes the inhibitory effect of this psychostimulant on the plasma testo sterone concentration in mice. On the other hand, a weak - if any - ef fect of L-NAME alone on corticosterone and testosterone levels suggest s that nitric oxide plays a minor role in the tonic regulation of thes e hormones' secretion.