The antianxiety-like effects of antagonists of group I and agonists of group II and III metabotropic glutamate receptors after intrahippocampal administration

Rationale: Substances acting as agonists of group II mGlu receptors with jo int group I mGlu receptor antagonist effects, or group II mGlu receptors ag onists, were shown to induce antianxiety- like effect in rats after intrahi ppocampal administration. Objective: The present study was undertaken to es tablish whether a more selective group I, II, III mGlu receptors agonists/a ntagonists induce anxiolytic-like effects after injection to the hippocampu s. Methods: (S)-4-Carboxyphenylglycine [(S)-4CPG] and 7-(hydroxyimino)cyclo propan [b]chromen-1 alpha -carboxylic ethyl ester (CPCCOEt), selective anta gonists at group I mGlu receptors, or (+)1S, 2S, 5R. 6S-2-aminobicyclo[3.1. 0]hexane-2,6-dicarboxylic acid (LY354740) and (2S, 1'S, 2'S)-2-(carboxycycl opropyl)glycine (L-CCG-I), two selective agonists of group II mGlu receptor s, as well as (1S, 2S, 4S, 5S)-2-aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I (ABHxD-I), an agonist at all three groups of mGlu receptors and L-s erine-O-phosphate (L-SOP), an agonist at group III mGlu receptors, were use d. All compounds were administered into the CAI region of the dorsal hippoc ampus. The conflict drinking Vogel test in rats was used to estimate the an xiolytic-like effects of all the compounds. Results: After intrahippocampal administration, both selective group I mGlu receptors antagonists (S)-4CPG and CPCCOEt, as well as the selective agonists of group II mGlu receptors LY 354740 and L-CCG-I, and an agonist of group III mGlu receptors, L-SOP, i nduced anticonflict effects. Conclusion: Selective antagonists of group I m Glu receptors and agonists of group II and group III mGlu receptors exhibit anxiolytic-like activity in the conflict drinking test. It seems that the hippocampus may be one of the brain structures involved in the anticonflict effect of mGlu receptor agonists/antagonists.