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 ester (L-NAME, 30 mg/kg i.p.), on morphine-induced changes in the plasma corticosterone and testosterone levels were studied in male mice. Acute morphine 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 increasing doses of morphine, from 15 to 50 mg/kg i.p., increased the plasma corticosterone concentration at 2 hr after the last injection. Single administration 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. Pretreatment of mice with L-NAME enhanced the stimulatory effects of both acute and repeated morphine administration on the corticosterone level. D-NAME (30 mg/kg i.p.), an inactive form of the nitric oxide synthase inhibitor, had no effect on the morphine-induced changes in the corticosterone level. Acute morphine administration had no effect on the plasma testosterone level after 1 or 2 hr, whereas repeated drug injections decreased the hormone concentration 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 the stimulatory effect of morphine on corticosterone secretion, but does not influence the inhibitory effect of repeated morphine on the plasma testosterone concentration in mice.