Putative anxiety-linked effects of the nitric oxide synthase inhibitor L-NAME in three murine exploratory behavior models.
The aim of the current study was to extend investigation into possible linkage between nitric oxide (NO) and anxiety-linked behavior using a battery of tests. Effects of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) were investigated in three murine models of anxiety-the light-dark, hole-board and elevated plus-maze-in between-groups designs. Treatment groups included L-NAME (0 [vehicle, or Veh], 10, 25, and 50 mg/kg) and 50 mg/kg of the inactive isomer N(G)-nitro-D-arginine methyl ester (D-NAME) injected subcutaneously. Mice exhibited a robust anxiogenic-like response profile reflected by dose-related decreases in both light-dark (transitions and time in lighted area) and hole-board (head dips and time spent head dipping) test measures, reaching statistical significance at 25 and 50 mg/kg L-NAME when compared to Veh controls (P<.05 or.01; Dunnett's t test), while distance traveled and rearing showed no significant differential pattern in either model. In both models, there was a strong dissociation between nonspecific locomotion and putative exploratory behaviors. D-NAME was not significantly different from Veh condition in either model, indicating a stereospecific action and supporting NO involvement. A dose-related decrease was also observed for several traditional and ethological measures in the plus-maze; however, the effect was limited and relatively weak or absent; with the exception of open-arm and percent open-arm entries, putative anxiety-sensitive measures reached statistical significance only at the highest dose. Reductions in motor activity compromised ability to dissociate an anxiety linkage from a nonspecific motor effect in most measures. It is concluded that the hole-board and light-dark tests provide indication of anxiogenic-like action of NOS inhibition, suggesting that NO has an anxiolytic action. Data from the plus-maze are unclear, owing to a confounding motor influence in most measures.
Czech
Donald A
DA
Biopsychology Laboratory, Department of Psychology, Marquette University, Milwaukee, WI 53201-1881, USA. Donald.Czech@marquette.edu
Jacobson
Erika B
EB
LeSueur-Reed
Kolitta T
KT
Kazel
Melanie R
MR
D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000201:enzymology / Q000523:psychology; D003624:Darkness; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D008029:Lighting; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester