Putative anxiety-linked effects of the nitric oxide synthase inhibitor l-NAME in three murine exploratory behavior models》.pdf

Pharmacology, Biochemistry and Behavior 75 (2003) 741–748 /locate/pharmbiochembeh Putative anxiety-linked effects of the nitric oxide synthase inhibitor L-NAME in three murine exploratory behavior models Donald A. Czech*, Erika B. Jacobson, Kolitta T. LeSueur-Reed, Melanie R. Kazel Biopsychology Laboratory, Department of Psychology, Marquette University, SC-454, P.O. Box 1881, Milwaukee, WI 53201-1881, USA Received 24 May 2002; received in revised form 10 March 2003; accepted 5 May 2003 Abstract 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 NG-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 NG-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