Nitric oxide synthase mediates delta opioid receptor-induced hypothermia in rats

The role of nitric oxide (NO) production in delta opioid receptor-induced hypothennia has not been reported The present study investigated the effect of nitric oxide synthase (NOS) inhibitors on the hypothermic effect of (+)-4-[(aR)-a-((2S,5R)4-allyl-2,5-dimethyl-1-piperazinyl)-3methoxybenzyl]-N,N-diethylbenzamide (SNC-80), a nonpeptide delta opioid agonist. SNC-80 (35 mg/kg, i.p.) administered to rats caused a significant hypothennia. N-nitro-(L)-arginine methyl ester ((L)-NAME) (10, 25 and 50 mg/kg, i.p.), a NOS inhibitor, and 7-nitroindazole (7-NI) (5 and 10 mg/kg, i.p.), a neuronal NOS inhibitor, were ineffective. For combined administration, (L)-NAME (50 mg/kg, i.p.) or 7-NI (10 mg/kg, i.p.) attenuated SNC-80-evoked hypothermia. To determine the involvement of central NOS, (L)-NAME (0.25, 0.5 and 1 mg/rat) was administered i.c.v. 30 min prior to SNC-80 (35 mg/kg, i.p.). Experiments revealed that (L)-NAME (1 mg/rat, i.c.v.) attenuated SNC-80-induced hypothermia. The present data demonstrate that central NO production is necessary for delta opioid receptor-induced hypothemua. (c) 2006 Elsevier B.V. All rights reserved.