Anxiolytic effect of nitric oxide synthase inhibitors microinjected into the dorsal central grey.
Nitric oxide synthase (NOS) accounts for most of the NADPH-diaphorase neuronal activity in the brain. NADPH-diaphorase-positive neurones have been localized at the dorso-lateral part of the periaqueductal grey (PAG), a region related to anxiety. Microinjections of the NOS inhibitors L-NAME (10-200 nmol 0.5 microliter-1) and L-NOARG (10-100 nmol) at this site induced anxiolytic-like effects in the elevated plus maze. These effects, however, occurred only at a limited range of doses and the dose-effect curve had a bell shape, higher doses of both compounds tending to be anxiogenic. The anxiolytic effect of L-NAME was antagonized by a previous microinjection of L-arginine (50 nmol 0.5 microliter-1). These results suggest that NO may play a role in PAG neurotransmission involved in anxiety.
Guimarães
F S
FS
Department of Pharmacology, FMRP, Ribeirão Preto, SP, Brazil.
de Aguiar
J C
JC
Del Bel
E A
EA
Ballejo
G
G
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006651:Histocytochemistry; D008297:Male; D008845:Microinjections; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000201:enzymology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010487:Periaqueductal Gray / Q000166:cytology / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
D014151:Anti-Anxiety Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester