Metabotropic glutamate receptors mediate cocaine relapse

代谢型谷氨酸受体介导可卡因复发

• 批准号: 7115921
• 负责人: JAMIE PETERS
• 金额: $ 3.21万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115921
• 关键词: behavioral /social science research tag; cocaine; craving; drug addiction; glutamate receptor; laboratory rat; nucleus accumbens; pathologic process; predoctoral investigator; prefrontal lobe /cortex; receptor binding; relapse /recurrence; stimulant /agonist

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.

描述（由申请人提供）： 伏隔核中的谷氨酸传输对于药物引发的复发模型中恢复可卡因寻求很重要。代谢型谷氨酸受体 (mGluR) 在可塑性诱导事件中调节谷氨酸能系统的活性。 II 类代谢型谷氨酸受体是 mGluR 的一个特别有趣的亚类。它们在突触前和突触后发挥作用，可被视为基础谷氨酸能张力的传感器以及突触活动的调节器。通过恢复伏隔核中的谷氨酸能张力（长期可卡因和戒断后基础谷氨酸水平降低），II 类 mGluR 激动剂可能具有治疗成瘾的潜力。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求行为所必需的。这些受体的全身激活也被证明可以减少焦虑并防止某些精神兴奋剂引起的行为。本研究旨在检查 II 组 mGluR 激动剂对可卡因诱导的可卡因寻求行为恢复的影响，并确定全身效应是否可归因于伏隔核受体的直接激动剂作用。