METABOTROPIC GLUTAMATE RECEPTORS IN COCAINE ABUSE AND RELAPSE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。越来越多的证据支持代谢型谷氨酸受体（mGluR）系统在可卡因滥用相关的行为效应中的作用。我们研究了选择性II组mGluR激动剂在可卡因自我给药和复发的非人灵长类动物模型中的影响。其他研究确定了可卡因配对刺激对激动剂有效性的影响以及选择性II组mGluR拮抗剂逆转激动剂作用的能力。研究人员对松鼠猴进行了训练，让它们在二阶强化计划下自我注射可卡因，在该计划中，药物注射与独特的视觉刺激配对。II组mGluR激动剂LY379268在存在和不存在可卡因配对刺激的情况下均减弱可卡因自我给药长达48小时，并且LY379268的作用被II组mGluR拮抗剂LY341495阻断。在随后的实验中，可卡因寻求被熄灭的可卡因注射替代车辆和省略可卡因配对刺激。LY379268减弱了在存在或不存在可卡因配对刺激的情况下由可卡因引发诱导的熄灭的可卡因寻求的恢复，并且该作用再次被LY341495阻断。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Growing evidence supports a role for metabotropic glutamate receptor (mGluR) systems in the behavioral effects of cocaine related to its abuse. We investigated the impact of a selective Group II mGluR agonist in nonhuman primate models of cocaine self-administration and relapse. Additional studies determined influence of a cocaine-paired stimulus on the effectiveness of the agonist as well as the ability of a selective Group II mGluR antagonist to reverse the effect of the agonist. Squirrel monkeys were trained to self-administer cocaine under a second-order schedule of reinforcement in which drug injections were paired with a distinctive visual stimulus. The Group II mGluR agonist LY379268 attenuated cocaine self-administration for up to 48 hours both in the presence and absence of the cocaine-paired stimulus, and the effects of LY379268 were blocked by the Group II mGluR antagonist LY341495. In subsequent experiments, cocaine seeking was extinguished by substituting vehicle for cocaine injections and omitting the cocaine-paired stimulus. LY379268 attenuated the reinstatement of extinguished cocaine seeking induced by cocaine priming both in the presence or absence of the cocaine-paired stimulus, and the effects were again blocked by LY341495.