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This study was supported by grants from Ministerio de Economia y Competitividad (grant SAF2016-75347R) and Plan Nacional sobre Drogas #2014I020, #2016I004). LDC received FPU grants from the Ministerio de Economía y Competitividad (15/02492). JC, LDC, EE, RLA and DP belong to the quality mentioned group 2017SGR979 by Generalitat de Catalunya. RLA position was funded by an institutional program of the

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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 ΔFosB.

3,4-methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with cocaine-like properties. In a previous work, we exposed adolescent mice to MDPV, finding sensitization to cocaine effects, and a higher vulnerability to cocaine abuse in adulthood. Here we sought to determine if such MDPV schedule induces additional behavioral-neuronal changes that could explain such results. After MDPV treatment (1.5 mg•kg-1 , twice daily, 7 days), mice were behaviorally tested. Also, we investigated protein changes in various brain regions MDPV induced aggressiveness and anxiety, but also contributed to a faster habituation to the open field. This feature co-occurred with an induction of ΔFosB in the orbitofrontal cortex that was higher than its expression in the ventral striatum. Early after treatment, D2R:D1R ratio pointed to a preponderance of D1R but, upon withdrawal, the ratio recovered. Increased expression of Arc, CDK5 and TH, and decrease in DAT protein levels persisted longer after withdrawal, pointing to a neuroplastic lasting effect similar to that involved in cocaine addiction. The implication of the hyperdopaminergic condition in the MDPV-induced aggressiveness cannot be ruled out. We also found an initial oxidative effect of MDPV, without glial activation. Moreover, although initially the dopaminergic signal induced by MDPV resulted in increased ΔFosB, we did not observe any change in NFκB or GluA2 expression. Finally, the changes observed after MDPV treatment could not be explained according to the autoregulatory loop between ΔFosB and the epigenetic repressor G9a described for cocaine. This provides new knowledge about the neuroadaptive changes involved in the vulnerability to psychostimulant addiction. *Manuscript Click here to view linked References W2, 2 days after the end of the treatment; W3, 3 days after the end of the treatment; W21, 21 days after the end of the treatment, is the end of the withdrawal.