Antidepressant- and anxiolytic-like effects of selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole in mice.
Various inhibitors of nitric oxide synthase (NOS) have been shown to possess antidepressant- and anxiolytic-like properties in animal models. The aim of this study was to compare the behavioural effects of NOS inhibitor 7-nitroindazole (7-NI) with the more selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)imidazole (TRIM) in animal models predictive of antidepressant- and anxiolytic-like activity in order to clarify the role of distinct isoforms of NOS in the regulation of depression and anxiety. Both TRIM (50 mg/kg) and 7-NI (50 mg/kg) decreased the immobility time in the forced swimming test. The magnitude of the effect was comparable to that of the tricyclic antidepressant imipramine (15 mg/kg). The antidepressant-like effect of TRIM was counteracted by pretreatment with L-arginine (250 mg/kg). The systemic administration of TRIM (50 mg/kg), but not 7-NI (up to 50 mg/kg) increased the time spent in the light side of the apparatus in the light-dark compartment test. The anxiolytic-like effect of TRIM was antagonised by pretreatment with L-arginine. Both TRIM and 7-NI decreased the locomotion of animals in the open field and caused motor incoordination on rotarod. These motor side effects were more pronounced in the case of 7-NI and were not diminished by pretreatment with L-arginine. We conclude that neuronal NOS seems to play the key role in the antidepressant- and anxiolytic-like effects of NOS inhibitors.
Volke
Vallo
V
Department of Physiology, University of Tartu, 19 Ravila Street, Estonia. vallov@ut.ee
Wegener
Gregers
G
Bourin
Michel
M
Vasar
Eero
E
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy; D001120:Arginine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007099:Imipramine / Q000494:pharmacology; D007103:Immobilization / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D011930:Reaction Time / Q000187:drug effects; D013550:Swimming
D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007191:Indazoles; C098186:1-(2-trifluoromethylphenyl)imidazole; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D007099:Imipramine; C080122:7-nitroindazole