mGlu5 receptor deletion reduces relapse to food-seeking and prevents the anti-relapse effects of mGlu5 receptor blockade in mice

Aims: Convergent data suggest that there is a hyperglutamatergic state that arises during relapse to drug seeking. Blockade of mGlu5 receptors provides one approach to dampening glutamate tone. However, the role of mGlu5 receptors in relapse to food seeking behavior has not been explored extensively and has not been scrutinized using receptor null mice. Main methods: Wild-type (WT) and mGlu5 receptor knockout (KO) mice were compared under the acquisition of a discriminated operant response maintained by food, during extinction of the response, and during the reinstatement of the response by food and food-associated stimuli. The impact of the mGlu5 receptor antagonist MTEP was investigated. Key findings: Acquisition and extinction were not markedly different in WT and KO mice. MTEP decreased response reinstatement in WT mice. This behavioral effect of MTEP was not present in the KO mice, demonstrating the dependence of the effect of MTEP on mGlu5 receptors. As with the effect of MTEP in WT mice, receptor deletion reduced response reinstatement in KO mice. Significance: This is the first report to evaluate the reinstatement of food-seeking in mGlu5 receptor KO mice. The data reported here add to those in the literature that support a role for mGlu5 receptors in the control of this relapse effect. The data also reinforce the potential utility of mGlu5 receptor antagonists in relapse prevention to food-seeking behaviors. (C) 2011 Elsevier Inc. All rights reserved.