Studies have also examined the effects of targeting mGlu2/3 receptors within the contexts of operant ethanol self-administration. When given systemically, the mGlu2/3 antagonist LY341495 did not alter operant responding for ethanol by P rats,134 although systemic pretreatment with the mGlu2/3 receptor agonist LY404039 reduced ethanol-seeking and -relapse-like behavior.145 However, these latter authors reported that LY404039 did not alter the maintenance of operant ethanol self-administration in these animals.145 Interestingly, the local application of the mGlu2/3 agonist LY379268 in the AcbCo was sufficient to reduce operant ethanol self-administration by P rats,141 in a manner akin to the aforementioned studies of mice drinking under free-access conditions in the home cage.120,123 While understudied, the effects of mGlu2/3 agonists appear to depend upon the route of administration or the experimental procedures employed. However, as observed with mGlu1 antagonists,134,135,143 the effect of intra-AcbCo mGlu2/3 agonism on operant ethanol drinking by P rats is also not specific due to effects on locomotor activity.141 Other lines of evidence support an important role for mGlu2 receptors in drug addiction as well.97,102,146
