BACKGROUND AND PURPOSE 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with powerful psychostimulant effects. It selectively inhibits the dopamine transporter (DAT) and is 10-50-fold more potent as a DAT blocker than cocaine, suggesting a high abuse liability. The main objective of the present study was to assess the consequences of an early (adolescence) MDPV exposure on the psychostimulant, rewarding and reinforcing effects induced by cocaine in adult mice. EXPERIMENTAL APPROACH Twenty-one days after MDPV pretreatment (1.5 mg.kg(-1), s.c., twice daily for 7 days), adult mice were tested with cocaine, using locomotor activity, conditioned place preference and self-administration (SA) paradigms. In parallel, dopamine D-2 receptor density and the expression of c-Fos and Delta FosB in the striatum were determined. KEY RESULTS MDPV treatment enhanced the psychostimulant and conditioning effects of cocaine. Acquisition of cocaine SA was unchanged in mice pretreated with MDPV, whereas the breaking point achieved under a progressive ratio programme and reinstatement after extinction were higher in this group of mice. MDPV decreased D2 receptor density but increased Delta FosB expression three-fold. As expected, acute cocaine increased c-Fos expression, but MDPV pretreatment negatively influenced its expression. Delta FosB accumulation declined during MDPV withdrawal, although it remained elevated in adult mice when tested for cocaine effects. CONCLUSION AND IMPLICATIONS MDPV exposure during adolescence induced long-lasting adaptive changes related to enhanced responsiveness to cocaine in the adult mice that seems to lead to a higher vulnerability to cocaine abuse. This particular behaviour correlated with increased expression of Delta FosB.