Differential effects of mGluR1 and mGlur5 antagonism on spatial learning in rats

The effects of selective mGluR1 and mGluR5 antagonists on long-term acquisition were tested in a spatial three-choice reward-finding test. Bilateral prelimbic injections of the mGluR1 antagonist, (S)-4-carboxyphenylglycine (4-CPG), before training sessions blocked acquisition of correct performance between sessions. Similar injections given after full training of a control group significantly impaired correct performance without causing a complete block. Pretraining injections (intraperitoneal or intravenous) of the systemically active mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), had no effect on long-term acquisition in the reward-finding task. In an open-field test, bilateral prelimbic pretest application of 4-CPG prevented normal adaptation of spontaneous exploration as seen in control animals. MPEP, on the other hand, had no effect. In conclusion, the results confirmed that mGluR1 is involved in spatial long-term acquisition and suggested an additional role in recall of acquired skills. Furthermore, it was concluded that antagonism of mGluR1 or mGluR5 had different effects both in the appetitive spatial task and in the open-field test.