Die Rolle metabotroper Glutamatrezeptoren der Gruppe I beim Lernen und Gedächtnis der Ratte

Rationale: The role of glutamatergic system inlearning and memory has been extensively studied, andespecially N-methyl-D-aspartate (NMDA) receptors havebeen implicated in different learning and memory proces-ses. Less is known, however, about group I metabotropicglutamate (mGlu) receptors in this field. Recent studiesindicated that the coactivation of both NMDA and group ImGlu receptors is required for the induction of long-termpotentiation (LTP) and learning. Objective: The purposeof the study is to evaluate if there is a functional interactionbetween NMDA and group I mGlu receptors in two differ-ent models of aversive learning. Methods: Effects ofNMDA, mGlu1, and mGlu5 receptor antagonists on ac-quisition were tested after systemic coadministration ofselected ineffective doses in passive avoidance (PA) andfear-potentiated startle (FPS). Results: Interaction in aver-sive learning was investigated using selective antagonists:(3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM) for mGlu1, [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) for mGlu5,and (+)-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate [(+)MK-801] for NMDA receptors. InPA, the coapplication of MTEP at a dose of 5 mg/kg and (+)MK-801 at a dose of 0.1 mg/kg 30 min before trainingimpaired the acquisition tested 24 h later. Similarly,EMQMCM (2.5 mg/kg) plus (+)MK-801 (0.1 mg/kg),given during the acquisition phase, blocked the acquisitionof the PA response. In contrast, neither the combination ofMTEP (1.25 mg/kg) nor EMQMCM (5 mg/kg) plus (+)MK-801 (0.05 mg/kg) was effective on the acquisitionassessed in the FPS paradigm. Conclusion: The findingssuggest differences in the interaction of the NMDA andmGlu group I receptor types in aversive instrumentalconditioning vs conditioning to a discrete light cue.