Participation of cholinergic system in memory deficits induced by blockade of hippocampal mGlu1 receptors

We investigated the role of hippocampal group I metabotropic glutamate receptors (mGlu1 receptors) in the retrieval process of spatial memory using 8-arm radial maze performance with 4 arms baited. In addition, the participation of the cholinergic system in memory deficits induced by mGlu1 receptors antagonist was studied. Intrahippocampal injection of (R,S)-1-Aminoindan-1,5-dicarboxylic acid (AIDA), a mGlu1 receptor antagonist, significantly increased total error, reference memory error and working memory error at a dose of 20 nmol/side. Donepezil (0.5 and 1.0 mg/kg, p.o.) showed an ameliorative effect on AIDA-induced memory deficits. Improvement by donepezil of AIDA-induced memory deficits was antagonized by scopolamine (5 nmol/side) but not by mecamylamine (200 nmol/side) at a dose that did not affect performance. These findings clearly indicate that hippocampal mGlu1 receptors play an important role in the retrieval of spatial memory. Furthermore, we found that hippocampal mGlu1 receptors were closely associated with muscarinic receptors in memory performance.