Cocaine addiction is a chronic disorder with a high relapse rate; therefore, it is a priority to understand the neural mechanisms involved in finding the drug during relapse to develop effective pharmacotherapies. Glutamate metabotropic receptor 5 (mGluR5) appears to be involved in key-induced reinstatement associated with cocaine. The main objective of this study was to deepen the role of the mGluR5 receptor in relapse in cocaine use, evaluating the effect of MPEP, a negative allosteric modulator of mGluR5, on the reinstatement induced by cocaine priming in the paradigm of location preference conditioning (CPL). OF1 mice (48 males and 48 females) were conditioned on the CPL paradigm with cocaine (20 mg/kg) and exposed to an extinction program. When the extinction of the conditioned preference was confirmed, the efficacy of MPEP (30 mg/kg) was evaluated to block successive reinstatements by priming cocaine into the CPL. Contingent administration of MPEP with cocaine in the CPL increased drug search behavior and the number of reinstatements. In addition, administration of MPEP alone resulted in cross-reinstatement in the cocaine-induced CPL. Therefore, the MPEP not only did not prevent, but also increased the reinstatements of the conditioned preference induced by cocaine priming. These results can help you understand the role of mGluR5 in relapse to cocaine use.