Inhibition of neuronal nitric oxide synthase (n-cNOS) reverses the corticotrophin-induced behavioral effects in rats.
The nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (N-NMMA) and the competitive substrate for NO synthase L-arginine were used to determine the role of endogenous NO on the behavioral and neuroendocrine responsiveness following systemic corticotrophin in dexamethasone-suppressed rats. Corticotrophin (50-200 mU/kg, s.c.) dose-dependently decreased behavioral activity in the actimeter and produced significant anxiolytic and anti-risk activity in the plus-maze behavior test, without affecting systolic blood pressure. Rats given corticotrophin showed significant increased plasma corticosterone and reduced adrenal ascorbic acid level. These behavioral and adrenal responses of corticotrophin were dose dependently blocked by metyrapone (20 and 50 mg/kg, i.p.), an inhibitor of steroid 11beta-hydroxylase in adrenal and neural tissues that block steroidogenesis. Intracerebroventricular administration of L-NMMA (20 microg/rat in 10 microl) significantly prevented the behavioral hypoactivity and anxiolytic-like responses of corticotrophin without influencing the adrenal responsiveness. The effect of L-NMMA was completely reversed by preadministration of L-arginine (300 mg/kg, i.p.). These results suggest that neuronal nitric oxide pathway plays an important modulating role in the behavioral effects of corticotrophin by mechanisms other than those involving cardiovascular effects.
Reddy
D S
DS
Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar
D009419:Nerve Tissue Proteins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat