Metabotropic glutamate receptors mediate cocaine relapse

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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.