Cross-reinstatement between 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using conditioned place preference.

3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) considered to be a cocaine-like psychostimulant. The substitution of an established illicit drug as cocaine with an NPS is a pattern of use reported among drug users. The aim of this study was to investigate the relationship between cocaine and MDPV in the reinstatement of the conditioned place preference (CPP) paradigm, in order to establish whether there is cross-reinstatement between the two psychostimulants. Four experimental groups of male OF1 mice were subjected to the CPP paradigm: MDPV-MDPV, Cocaine-Cocaine, Cocaine-MDPV, and MDPV-Cocaine. The first drug refers to the substance with which the animals were conditioned (cocaine 10 mg/kg or MDPV 2 mg/kg) and the s to the substance with which preference was reinstated. In parallel, G9a, ΔFosB, CB1 receptor, CDK5, Arc and c-Fos were determined in ventral striatum. MDPV induced CPP at doses from 1 to 4 mg/kg. Although 2 mg/kg MDPV induced a stronger psychostimulant effect than 10 mg/kg cocaine, both doses seemed to be equivalent in their rewarding properties. However, memories associated with MDPV required more time to be extinguished. MDPV and cocaine restore drug-seeking behavior with respect to each other, although relapse into drug-taking is always more pronounced with the conditioning drug. The fact that MDPV-treated mice show increased ΔFosB protein levels correlates with its longer extinction time and points to the activation of neuroplasticity mechanisms that persist for at least 12 days. Moreover, in these animals, a priming-dose of cocaine can trigger significant neuroplasticity, implying a high vulnerability to cocaine abuse.