Role of the Nitric-Oxide Synthase Isoforms during Morphine-Induced Hyperthermia in Rats

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Abstract
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.