Effect of central and peripheral administration of a nitric oxide synthase inhibitor on morphine hyperthermia in rats

The effect of central and peripheral administration of a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on morphine hyperthermia was studied in male Sprague-Dawley rats. The first series of experiments examined the effect of subcutaneous (s.c.) administration of L-NAME on the hyperthermia induced by morphine given s.c. in doses of 4 and 15 mg/kg. L-NAME, at a s.c. dose of 50 mg/kg, per se, had no influence on body temperature (T(b)). Coadministration of L-NAME (50 mg/kg, s.c.) with the higher dose of morphine (15 mg/kg, s.c.) caused a significant suppression of morphine hyperthermia during the first 30 min and then produced hypothermia. In contrast, s.c. injection of L-NAME (50 mg/kg, s.c.) failed to alter the hyperthermic response induced by the lower dose of morphine (4 mg/kg). In the second series of experiments, we investigated the effect of intracerebroventricular (i.c.v.) administration of L-NAME on the hyperthermia induced by morphine given s.c. L-NAME, itself, given i.c.v. at a dose of 1 mg did not evoke any change in T(b). Intracerebroventricular administration of L-NAME (1 mg) blocked the hyperthermia induced by 15 mg/kg morphine during the first 30 min and induced a slight hypothermia but did not alter the hyperthermia induced by 4 mg/kg morphine. The results indicate that either central or peripheral NO synthesis is required for the production of hyperthermia induced by 15 mg/kg of morphine. However, NO synthesis does not seem to be involved in the hyperthermic process induced by 4 mg/kg of morphine.