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.
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