The effect of N-nitro-L-arginine methyl ester on morphine-induced changes in the plasma corticosterone and testosterone levels in mice

Effects of the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl e ster (L-NAME, 30 mg/kg i.p.), on morphine-induced changes in the plasma cor ticosterone and testosterone levels were studied in male mice. Acute morphi ne administration (15 and 30 mg/kg i.p.) enhanced the corticosterone level after 1 and 2 hr (at a dose of 30 mg/kg only). A 4-day treatment with incre asing doses of morphine, from 15 to 50 mg/kg i.p., increased the plasma cor ticosterone concentration at 2 hr after the last injection. Single administ ration of L-NAME (30 mg/kg i.p.) had no effect on the 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. Pretreatme nt of mice with L-NAME enhanced the stimulatory effects of both acute and r epeated morphine administration on the corticosterone level. D-NAME (30 mg/ kg i.p.), an inactive form of the nitric oxide synthase inhibitor, had no e ffect on the morphine-induced changes in the corticosterone level. Acute mo rphine administration had no effect on the plasma testosterone level after 1 or 2 hr, whereas repeated drug injections decreased the hormone concentra tion after 2 hr. Single or repeated L-NAME administration did not influence the testosterone level in either control or morphine-treated animals. The above results indicate that inhibition of nitric oxide synthase enhances th e stimulatory effect of morphine on corticosterone secretion, but does not influence the inhibitory effect of repeated morphine on the plasma testoste rone concentration in mice.