Functional interaction of NMDA and group I metabotropic glutamate receptors in negatively reinforced learning in rats |
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Authors: | A Gravius M Pietraszek W J Schmidt W Danysz |
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Institution: | (1) Preclinical R&D, Merz Pharmaceuticals, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany;(2) Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Cracow, Poland;(3) Department of Neuropharmacology, Zoological Institute, University of Tübingen, Tübingen, Germany |
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Abstract: | Rationale The role of glutamatergic system in learning and memory has been extensively studied, and especially N-methyl-d-aspartate (NMDA) receptors have been implicated in different learning and memory processes. Less is known, however, about
group I metabotropic glutamate (mGlu) receptors in this field. Recent studies indicated that the coactivation of both NMDA
and group I mGlu receptors is required for the induction of long-term potentiation (LTP) and learning.
Objective The purpose of the study is to evaluate if there is a functional interaction between NMDA and group I mGlu receptors in two
different models of aversive learning.
Methods Effects of NMDA, mGlu1, and mGlu5 receptor antagonists on acquisition were tested after systemic coadministration of selected
ineffective doses in passive avoidance (PA) and fear-potentiated startle (FPS).
Results Interaction in aversive 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. In PA, 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 training impaired 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 acquisition of the PA response. In contrast, neither the combination of MTEP
(1.25 mg/kg) nor EMQMCM (5 mg/kg) plus (+)MK-801 (0.05 mg/kg) was effective on the acquisition assessed in the FPS paradigm.
Conclusion The findings suggest differences in the interaction of the NMDA and mGlu group I receptor types in aversive instrumental conditioning
vs conditioning to a discrete light cue. |
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Keywords: | mGlu1 receptor antagonist mGlu5 receptor antagonist NMDA receptor antagonist Acquisition Fear-potentiated startle Passive avoidance |
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