Metabotropic glutamate receptors in spatial and nonspatial learning in rats studied by means of agonist and antagonist application.

Abstract

We examined the effects of both the metabotropic glutamate receptor (mGluR) antagonist MCPG and the agonist tADA in two behavioral paradigms in rats: (1) brightness discrimination and (2) spatial alternation. Compounds were applied intracerebroventricularly at different times, either 30 min prior to training or immediately after training, and rats were tested for retention 24 hr later in the same paradigms. Both MCPG and tADA caused amnesia in the spatial alternation test, when applied pretraining, but no effect was obtained in the brightness discrimination paradigm. Drug-induced amnesia was shown not to be attributable to state-dependent effects of MCPG or tADA. Moreover, the memory inhibiting effect of MCPG was dose dependent, with a low dose (20 mM/5 ml) having no effect on learning and memory and a 10 times higher concentration (200 mM/5 ml) causing complete amnesia. Application of both saline and MCPG immediately post-training prevented memory formation, which may be attributable to an interference by the injection procedure with the process of memory formation. The mGluR agonist tADA, however, facilitated memory formation in the spatial alternation task, when injected immediately after training. Post-training application of the compounds had no effect on retention in the brightness discrimination task. On the basis of these data we conclude that (1) mGluRs are of particular importance for spatial learning and play no role in visual discrimination; (2) both the block and the activation of mGluRs inhibit spatial learning, suggesting that saturated activation prevents further modulation of mGluRs, which may be required during learning or memory formation; and (3) mGluR agonist tADA may be memory facilitating when applied after training, thus enhancing the establishment of the memory trace.