Allosteric enhancement of metabotropic glutamate receptor 5 function promotes spatial memory

Group I metabotropic glutamate receptors (mGluRs) have been implicated in learning and memory formation. Recent findings indicate an important function of the group I mGIuR subtype 5. Here, We used the Y-maze spatial alternation task and examined whether enhancement of intrinsic mGIuR5 activity immediately after learning, i.e. during a critical period for memory consolidation, would have any consequences on long-term memory retention in rats. Intracerebroventricular application of the allosteric mGIuR5 potentiator DFB (3,3'-difluorobenzaldazine) resulted in a marked improvement in spatial alternation retention when it was tested 24 h after training. The promnesic effect increased with the difficulty of the task and was apparently due to a substantial enhancement of consolidation. The applied dose of DFB did not cause behavioral changes in the open field, and was devoid of structural side-effects as evaluated by immunohistochemical examination. Our results suggest an important function of post-training mGIuR5 activation in some types of hippocampus-dependent spatial learning. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.