Effects of the metabotropic glutamate receptor antagonist MCPG on spatial and context-specific learning

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Abstract

The effects of the metabotropic glutamate receptor antagonist (+)-α-methyl-4-carboxyphenylglycine (MCPG) on performance in a water maze and in context-specific associative learning were examined in rats previously implanted with cannulae. MCPG (20.8 μg) injected intraventricularly (i.c.v.) before testing impaired the performance of rats in the spatial version of the Morris water maze, but 1/10 of this dose did not. Memory retention, evaluated 24 hr post-training, was also affected 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 further characterized on performance in another hippocampus-dependent spatial learning task, the context-dependent fear conditioning task. MCPG (20.8 μg, i.c.v.) did not interfere with conditioned freezing to context in this task. For comparison, a group of rats was injected with the NMDA receptor blocker MK801. MK801 at a dose that disrupted the performance in the spatial version of the Morris water maze (0.08 mg/kg), significantly reduced freezing compared to controls. These experiments indicate that MCPG-sensitive metabotropic receptors may be required for only a restricted subset of spatial learning tasks, while NMDA receptors may play an integral role in all spatial learning.

Section snippets

Animals and surgery

Male Lister–Hooded rats, weighing 250–275 g at the time of arrival, were used. They were provided with free access to lab. chow and water and were maintained on a 12:12 hr light–dark cycle (lights on at 06:00 hr). After at least 1 week of acclimatization, animals underwent surgery. Unilateral stainless steel guide cannulae (26-gauge) were implanted stereotaxically into the right lateral ventricle under pentobarbital anesthesia (50 mg/kg i.p.) using the atlas of Paxinos and Watson (1986)(coordinates:

Morris water maze

During the 4 days of training, both the MCPG-treated (at the high dose) and control animals showed significant improvement in performance, indicated by the decrease in both the time of reaching the platform [F(3,108)=107.5; p<0.01] and the distance of the animal from the platform [F(3,108)=77.4; p<0.01] (Fig. 1). Animals given MCPG, however, were significantly slower to learn the task. MCPG-treated rats took longer to reach the platform [F(1,35)=9.6; p<0.01] and their distance from the platform

Discussion

In the present study, the metabotropic glutamate receptor antagonist MCPG affected the performance of rats in the spatial version of the water maze. These results are in agreement with previous findings that showed disruption of learning by MCPG at the same dose in both a water maze task (Richter-Levin et al., 1994) and a Y-maze with footshock reinforcement (Riedel et al., 1994). We extend these findings by showing that a 10-fold lower dose of MCPG (2.1 μg) is without effect in the water maze

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