Anxiolytic-like activity of MGS0039,a selective group II mGlu receptor antagonist,is serotonin-and GABA-dependent

In the present study,we examined the anxiolytic-like effects of (1r,2r,3r,5r,6r)-2-amino-3-(3,4-dichlorobenzyloxy)-6fluorobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (mgs0039),a mglur2/3 antagonist,in the vogel conflict drinking test in rats. mgs0039 administered at the doses of 1 and 2 mg/kg ip (yet not at 3 mg/kg) produced anxiolytic-like effects in this test. diazepam (2.5-10 mg/kg) was used as a reference drug. in the second part of our experiment,mgs0039 was tested at an effective dose of 2 mg/kg after a mixed injection with ritanserin (5-ht2a/c receptor antagonist) and way100635 (5-ht1a receptor antagonist) or flumazenil (benzodiazepine receptor antagonist),and all of the compounds were found to attenuate the effect of mgs0039. the above results indicate that the mglur2/3 antagonist mgs0039 may play a role in the therapy of anxiety and that its action may be mediated by serotonin and the gabaergic systems. copyright © 2011 by institute of pharmacology polish academy of sciences.