Differential roles of mGlu₇ and mGlu₈ in amygdala-dependent behavior and physiology

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• 作者：Markus Fendt ; Stefan Imobersteg ; Daniel Peterlik ; Fr¨¦d¨¦rique Chaperon ; Catherine Mattes ; Christina Wittmann ; Hans-Rudolf Olpe ; Johannes Mosbacher ; Ivo Vranesic ; Herman van der Putten ; Kevin H. McAllister ; Peter J. Flor ; Christine E. Gee
• 关键词：AMN082 ; Anxiety ; Contextual fear ; DCPG ; Fear learning ; Glutamate
• 刊名：Neuropharmacology
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：72
• 期：Complete
• 页码：215-223
• 全文大小：1807 K

文摘

Glutamate transmission and synaptic plasticity in the amygdala are essential for the learning and expression of conditioned fear. Glutamate activates both ionotropic glutamate receptors and eight subtypes of metabotropic glutamate receptors (mGlu_1-8). In the present study, we investigated the roles of mGlu₇ and mGlu₈ in amygdala-dependent behavior and synaptic plasticity. We show that ablation of mGlu₇ but not mGlu₈ attenuates long-term potentiation (LTP) at thalamo-lateral amygdala (LA) synapses where a strong association between LTP and learning has been demonstrated. mGlu₇-deficient mice express a general deficit in conditioned fear whereas mGlu₈-deficient mice show a dramatic reduction in contextual fear. The mGlu₇ agonist AMN082 reduced thalamo-LA LTP and intra-amygdala administration blocked conditioned fear learning. In contrast, the mGlu₈ agonist DCPG decreased synaptic transmission but not LTP at thalamo-LA synapses. Intra-amygdala DCPG selectively reduced the expression of contextual fear but did not affect the acquisition and expression of cued fear. Taken together, these data revealed very different roles for mGlu₇ and mGlu₈ in amygdala synaptic transmission, fear learning and its expression. These receptors seem promising targets for treating anxiety disorders with different underlying pathologies with exaggerated fear learning (mGlu₇) or contextual fear (mGlu₈).