NMDA/glutamate mechanism of anxiolytic-like action of zinc in Vogel conflict test in mice

Abstract

Abstract--The objective of our study is to investigate the possible anxiolytic-like effect of zinc using one of the most useful animal models of anxiety, which is the Vogel conflict test (VCT) and to investigate the possible involvement of the glutamatergic system and NMDA receptors in this postulated effect. The anxiolytic-like effect of ZnCl 2 (20 mg/kg, i.p.) in the VCT was abolished by the pretreatment of animals with N-methyl-D-Aspartic acid (75 mg/kg, i.p., NMDA receptor agonist) that per se produced no effect in VCT. Moreover, the treatment of mice with CGP37849 (0.3 mg/kg, i.p., a competitive NMDA receptor antagonist) or MK-801 (0.05 mg/kg, i.p., a non-competitive NMDA receptor antagonist) was able to potentiate the action of sub-effective dose of ZnCl 2 (10 mg/kg, i.p.). Overall results indicate that zinc induces the anxiolytic-like effect in mice without development of tolerance and inhibition of the NMDA receptor activity is involved in the mechanism of this effect.