Inhibition of group I metabotropic glutamate receptors blocks spatial learning in rats

Abstract

Metabotropic glutamate receptors (mGluRs) are postulated to play a role in long-term potentiation and in learning and memory-formation. Previously, we found that the group I/II mGluR antagonist, (RS)- α-methyl-4-carboxyphenylglycine (MCPG), blocks Y-maze spatial alternation learning. In this study, we tested the group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) in comparison with MCPG using the same behavioural paradigm. Male Wistar rats were intracerebroventricularly injected with either 29 μg 4-CPG or 209 μg MCPG, 30 min prior to learning. Neither 4-CPG nor MCPG had an effect on spatial alternation performance in the training session. In the memory-retention test 24 h later, however, both the 4-CPG- and the MCPG-treated animals were strongly impaired compared with NaCl-injected control rats. These results suggest a particular importance of group I mGluRs in spatial memory-formation and indicate that MCPG effects found in previous learning experiments were predominantly due to an action at group I mGluRs.