Cannabidiol modulates the motivational and anxiety-like effects of 3,4-methylenedioxypyrovalerone (MDPV) in mice

3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) and the most widespread and life-threatening synthetic cathinone of the "bath salts". Preclinical research has proven the cocaine-like psychostimulant effects of MDPV and its potential for abuse. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid that has emerged as a new potential treatment for drug addiction. Here, we tested the effects of CBD (20 mg/kg) on MDPV (2 mg/kg)-induced conditioned place preference and MDPV (0.05 and 0.075 mg/kg/infusion) self-administration paradigms. In addition, we assessed the effects of the co-administration of CBD and MDPV (3 and 4 mg/kg) on anxiety-like behaviour using the elevated plus maze (EPM). CBD mitigated the MDPV-induced conditioned place preference. On the contrary, CBD administration throughout the MDPV (0.075 mg/kg/infusion) self-administration increased drug-seeking and taking behaviours, but only in the high-responders group of mice. Furthermore, CBD exerted anxiolytic-like effects, exclusively in MDPV-treated mice. Taken together, our results indicate that CBD modulation of MDPV-induced motivational responses in mice varies depending on the requirements of the learning task, resulting in a complex response. Therefore, further research attempting to decipher the behavioural and molecular interactions between CBD and MDPV is needed. This work was supported by Ministerio de Economía y Competitividad (grant number SAF2016-75966-R-FEDER and PID2019-104077-RB-100), Ministerio de Sanidad, Asuntos Sociales e Igualdad (Retic-ISCIII-RD/16/0017/0010-FEDER and Plan Nacional Sobre Drogas (#2018/007). L.A.-Z. received FPI grant (BES-2017-080066) from the Ministerio de Economía y Competitividad. The Department of Experimental and Health Sciences (UPF) is a “Unidad de Excelencia María de Maeztu” funded by the AEI (CEX2018-000792-M).