Group I metabotropic glutamate receptors (mGluRs)含有mGluR1及mGluR5 subtypes，其被認為和突觸塑性與學習記憶具有密切的相關性。近年來於電生理學與藥理學的研究顯示，mGluR5 subtype為恐懼記憶形成過程中所必需，但其在恐懼記憶消除中所扮演的角色卻未被探究。我們在受測鼠接受恐懼消除訓練(extinction training)前三十分鐘微量注射group 1 mGluR antagonists於其兩側的杏仁核中，結果發現mGluR5 antagonist會干擾恐懼消除訓練的學習與記憶；相對地，投予低劑量之group 1 mGluR agonist S-DHPG則可以促進此作用(facilitate extinction)，使動物體對於CS的恐懼反應降低。另一方面，即使未經過恐懼消除訓練的學習，微量注射S-DHPG於受測鼠杏仁核腦區仍可以減弱恐懼反應的表現，且此作用呈現dose-dependent現象，同時證明亦由mGluR5，而非mGluR1所媒介。我們進一步由高頻電刺激的實驗推測，mGluR5所誘導之恐懼反應降低的機制可能是藉由干擾AMPA receptors的磷酸化路徑，影響AMPA receptors在突觸細胞膜上之表現量，而改變突觸塑性與記憶的訊息傳遞路徑。綜合上述之結果顯示，杏仁核腦區之mGluR5亦為恐懼記憶消除過程中所必需，且mGluR5的活化可降低受測鼠之恐懼反應，其致效劑或許可運用於重度焦慮症，如創傷後壓力症候群之治療及用藥開發。

Group I metabotropic glutamate receptors (mGluRs) including mGluR1 and 5 are thought to be crucial for synaptic plasticity and learning and memory. Electrophysiological and pharmacological experiments have recently shown that the mGluR5 subtype is required for the acquisition of fear memory, but its role in memory extinction has not been determined. Rats were infused with group I mGluR antagonists bilaterally into the amygdala 30 min before extinction training, and memory retention was assessed 24 h later. We found that infusion of antagonist for mGluR5 but not mGluR1 impaired extinction. Conversely, pre-extinction injections of low-dose group I mGluR agonist S-DHPG facilitated extinction. Furthermore, S-DHPG reduced fear-potentiated startle in a dose-dependent manner, and the effect was blocked by the selective mGluR5 antagonist MPEP. Finally, we clarified the mechanisms involved in the DHPG-mediated fear extinction by tetanic stimulation (TS) experiments. S-DHPG attenuated TS-induced increase in surface GluR1 and reduced the activity of proteins that are involved in the phosphorylation of GluR1. The effects of S-DHPG were blocked by MPEP but not by CPCCOEt, indicating the mediation by mGluR5 rather than by mGluR1. Collectively, these results reveal that activation of mGluR5 is required for fear extinction, and it could reduce fear-potentiated startle after consolidation of fear memory. Thus, mGluR5 agonists may be used to treat excessive anxiety such as post-traumatic stress disorders.

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