Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/148191
Title: Neuroadaptive changes and behavioral effects after a sensitization regime of MDPV
Author: Duart Castells, Leticia
López Arnau, Raúl
Buenrostro Jáuregui, Mario
Muñoz-Villegas, P.
Valverde, O.
Camarasa, J.
Pubill Sánchez, David
Escubedo Rafa, Elena
Keywords: Cocaïna
Dopamina
Amfetamines
Ratolins
Drogues de disseny
Cocaine
Dopamine
Amphetamines
Mice
Designer drugs
Issue Date: 12-Oct-2018
Publisher: Elsevier Ltd
Abstract: 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.
Note: Versió postprint del document publicat a: https://doi.org/10.1016/j.neuropharm.2018.10.005
It is part of: Neuropharmacology, 2018, vol. 144, p. 271-281
URI: http://hdl.handle.net/2445/148191
Related resource: https://doi.org/10.1016/j.neuropharm.2018.10.005
ISSN: 0028-3908
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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