Antidepressant- and anxiolytic-like effects of selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole in mice - PubMed (original) (raw)

Comparative Study

. 2003 Mar 18;140(1-2):141-7.

doi: 10.1016/s0166-4328(02)00312-1.

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Comparative Study

Antidepressant- and anxiolytic-like effects of selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole in mice

Vallo Volke et al. Behav Brain Res. 2003.

Abstract

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.

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