Effects of the metabotropic glutamate receptor antagonist MCPG on spatial and context-specific 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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Role of metabotropic glutamate receptors in persistent forms of hippocampal plasticity and learning
2013, NeuropharmacologyCitation Excerpt :Co-application of an mGlu5 antagonist with an antagonist of group II mGlu receptors prevents object recognition memory using mechanisms that also involve the perirhinal cortex (Barker et al., 2006). Possible joint effects of these receptors were described using first generation mGlu antagonists, such as MCPG (α-methyl-4-carboxyphenylglycine), where impairments of spatial alternation performance (Riedel et al. 199b) and spatial learning in the water maze were reported (Richter-Levin et al., 1994; Bordi et al., 1996). Application of an mGlu5 PAM, 2-methyl-6- (phenylethynyl) pyridine (MPEP), prevents object-place learning (Popkirov and Manahan-Vaughan, 2011).
Contextual learning induces an increase in the number of hippocampal CA1 neurons expressing high levels of BDNF
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2007, Journal of Biological ChemistryCitation Excerpt :We have replicated the NMDA receptor dependence of contextual fear conditioning to determine whether the learning-induced alterations in GluR1 phosphorylation were dependent on NMDA receptor activation similar to the GluR1 phosphorylation during LTP. The NMDA receptor antagonist MK-801 blocked contextual fear conditioning in a dose-dependent manner as has been previously demonstrated (Fig. 2C) (58, 59). Footshock alone does not induce GluR1 phosphorylation.