Other mGluR ligands have also been tested for their effects on excessive ethanol drinking or ethanol reinforcement. Earlier studies revealed that systemic pretreatment with the selective mGlu1 antagonist, (−)-ethyl (7E)-7-hydroxyimino-1,7a-dihydrocyclopropa[b]chromene-1a-carboxylate (CPCCOEt), produced inconsistent effects on operant ethanol self-administration in P rats134 versus C57BL/6J mice,137 such that intra-Acb infusions of CPCCOEt were unable to alter binge drinking in mice.83 These inconsistent effects of CPCCOEt on measures of alcohol intake likely reflect its relative insolubility. For instance, the more soluble, highly selective, mGlu1 antagonist JNJ 16259685 lowers operant ethanol self-administration and ethanol breakpoint in P rats when administered systemically135,143 and reduces binge drinking when infused into the AcbSh of mice.144 However, systemic JNJ 16259685 pretreatment has nonselective effects in that it also reduces locomotor activity,135,143 which may reflect the high abundance of mGlu1 receptors in the cerebellum and their effects on its control of motor movement.134,135,143
