Nitric oxide synthase mediates delta opioid receptor-induced hypothermia in rats.
The role of nitric oxide (NO) production in delta opioid receptor-induced hypothermia 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)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80), a nonpeptide delta opioid agonist. SNC-80 (35 mg/kg, i.p.) administered to rats caused a significant hypothermia. 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 hypothermia.
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA, 19140, USA. scott.rawls@temple.edu
Scott M
SM
Rawls
Christine
C
Allebach
Alan
A
Cowan
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007035:Hypothermia / Q000201:enzymology / Q000503:physiopathology*; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*
D001549:Benzamides; D004791:Enzyme Inhibitors; D007191:Indazoles; D010879:Piperazines; D017465:Receptors, Opioid, delta; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester