Metabotropic glutamate receptors mediate cocaine relapse

描述(由申请人提供)： 伏核中谷氨酸的传递对于药物诱导的复吸模型恢复可卡因寻找具有重要意义。代谢性谷氨酸受体(MGluRs)在可塑性诱导事件中调节谷氨酸能系统的活动。第二类代谢性谷氨酸受体是mGluRs的一个特别有趣的亚类。它们既有突触前和突触后的作用，也可以被视为基础谷氨酸能张力的感受器和突触活动的调节器。通过恢复伏核的谷氨酸能张力，在慢性可卡因和戒断后基础谷氨酸水平降低，II组mGluR激动剂可能在治疗成瘾方面具有治疗潜力。这些受体的激活可以抑制谷氨酸的释放，谷氨酸的释放是伏隔核恢复药物寻找行为所必需的。这些受体的系统激活也被证明可以减少焦虑，防止某些精神刺激剂诱导的行为。本研究旨在研究第二组mGluR激动剂对可卡因诱导的可卡因寻找行为恢复的影响，并确定这种全身性效应是否可归因于伏核受体的直接激动剂作用。

DESCRIPTION (provided by applicant): Glutamate transmission in nucleus accumbens is important for reinstatement of cocaine-seeking in drug-primed models of relapse. Metabotropic glutamate receptors (mGluRs) modulate activity of glutamatergic systems during plasticity-inducing events. Group II metabotropic glutamate receptors are an especially interesting subclass of mGluRs. They act both pre- and postsynaptically and may be viewed as sensors for basal glutamatergic tone as well as modulators of synaptic activity. By restoring glutamatergic tone in the nucleus accumbens, where basal glutamate levels are reduced following chronic cocaine and withdrawal, group II mGluR agonists may have therapeutic potential in the treatment of addiction. Activation of these receptors can inhibit glutamate release, a requisite in nucleus accumbens for reinstatement of drug-seeking behavior. Systemic activation of these receptors has also been shown to reduce anxiety and to prevent certain psychostimulant-induced behaviors. This study proposes to examine the effects of group II mGluR agonists on cocaine-induced reinstatement of cocaine-seeking behavior and to determine if the systemic effects can be attributed to direct agonist action on receptors in the nucleus accumbens.