Role of the Nitric Oxide Pathway in κ-Opioid-Induced Hypothermia in Rats
- Center for Substance Abuse Research and Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania
- Dr. Khalid Benamar, Department of Pharmacology, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, PA 19140. E-mail address:kbenamar{at}hotmail.com
Abstract
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 κ-opioid receptor agonisttrans-(±)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.
Footnotes
-
This work was supported by Grants DA00376 and DA13429 from the National Institute on Drug Abuse (Bethesda, MD).
-
DOI: 10.1124/jpet.102.036269
- Abbreviations:
- Tb
- body temperature
- NO
- nitric oxide
- NOS
- nitric-oxide synthase
- U50,488H
- trans-(±)3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)-benzeneacetamide methane sulfate
- l-NAME
- N-nitro-l-arginine methyl ester
- POAH
- preoptic anterior hypothalamus
- CNS
- central nervous system
-
- Received March 14, 2002.
- Accepted June 25, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
