Role of the nitric oxide pathway in kappa-opioid-induced hypothermia in rats.
The effect of central and peripheral administration of a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the hypothermia induced by the selective kappa-opioid receptor agonist trans-(+/-)3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide methane sulfate (U50,488H) was studied in male Sprague-Dawley rats. In the first series of experiments, we examined the effect of subcutaneous (s.c.) administration of L-NAME on the hypothermia induced by s.c. injection of U50,488H. L-NAME, at a dose of 50 mg/kg s.c., had no influence on body temperature (Tb). Coadministration of L-NAME (50 mg/kg, s.c.) with U50,488H (10 mg/kg, s.c.) blocked the hypothermia induced by U50,488H. In the second series of experiments, we investigated the effect of intracerebroventricular (i.c.v.) administration of L-NAME on the hypothermia induced by s.c. injection of U50,488H. L-NAME itself, given i.c.v. at a dose of 1 mg/rat, did not evoke any change in Tb. Administration of L-NAME (1 mg/rat, i.c.v.) caused a significant suppression of U50,488H hypothermia. The results indicate that either central or peripheral nitric oxide synthesis is required for the production of hypothermia induced by U50,488H.
Benamar
Khalid
K
Center for Substance Abuse Research and Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. kbenamar@hotmail.com
Geller
Ellen B
EB
Adler
Martin W
MW
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000503:physiopathology; D007035:Hypothermia / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000502:physiology*
D018712:Analgesics, Non-Narcotic; D017473:Receptors, Opioid, kappa; D009569:Nitric Oxide; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D019331:NG-Nitroarginine Methyl Ester