Role of the nitric-oxide synthase isoforms during morphine-induced hyperthermia in rats

Recently, we demonstrated that the diffusible messenger molecule nitric oxide ( NO) is involved in the hyperthermic response induced by morphine by using a nonselective nitric-oxide synthase inhibitor, N-nitro-L-arginine methyl ester. The present work extended these studies to include 7-nitroindazole(7-NI), an inhibitor specific for neuronal nitric-oxide synthase ( nNOS), N(5)-(-iminoethyl)-L-ornithine (L-NIO), an inhibitor of endothelial NOS ( eNOS), and aminoguanidine (AG), a potent inhibitor of inducible NOS ( iNOS). A biotelemetry system was used in this study to measure the body temperature (Tb). A dose of 7-NI ( 5 or 10 mg/kg), which did not affect Tb by itself, blocked the hyperthermia induced by morphine in a dose-dependent manner ( 15 mg/kg i.p.). However, pretreatment with L-NIO (10-20 mg/kg) or with AG ( 50 mg/kg) failed to alter the hyperthermia induced by morphine. L-NIO ( 10-20 mg/kg) or AG ( 50 mg/kg) had no effect on Tb. These results suggest the involvement of nNOS in morphine-induced hyperthermia.