EFFECTS OF THE METABOTROPIC GLUTAMATE-RECEPTOR ANTAGONIST MCPG ON SPATIAL AND CONTEXT-SPECIFIC LEARNING

The effects of the metabotropic glutamate receptor antagonist (+)-alph a-methyl-4-carboxyphenylglycine (MCPG) on performance in a water maze and in context-specific associative learning were examined in rats pre viously implanted with cannulae. MCPG (20.8 mu g) injected intraventri cularly (i.c.v.) before testing impaired the performance of rats in th e spatial version of the Morris water maze, but 1/10 of this dose did not. Memory retention, evaluated 24 hr post-training, was also affecte d by the high dose of MCPG. However, performance in a cued version of the water maze was not impaired by the high dose, excluding effects of the drug on perceptual faculties. The effects of the MCPG were furthe r characterized on performance in another hippocampus-dependent spatia l learning task, the context-dependent fear conditioning task. MCPG (2 0.8 mu g, i.c.v.) did not interfere with conditioned freezing to conte xt in this task. For comparison, a group of rats was injected with the NMDA receptor blocker MK801. MK801 at a dose that disrupted the perfo rmance in the spatial version of the Morris water maze (0.08 mg/kg), s ignificantly reduced freezing compared to controls. These experiments indicate that MCPG-sensitive metabotropic receptors may be required fo r only a restricted subset of spatial learning tasks, while NMDA recep tors may play an integral role in all spatial learning. Copyright (C) 1996 Published by Elsevier Science Ltd.