title: The combination of MDPV and ethanol results in decreased cathinone and increased alcohol levels. Study of such pharmacological interaction.
abstract: Methylenedioxypyrovalerone (MDPV) is a new psychostimulant cathinone acting as a selective dopamine transporter blocker. Due to the concomitant consumption of ethanol (EtOH) and new psychoactive substances, it is of interest to explore a possible pharmacological interaction between MDPV and EtOH. In locomotor activity assays, EtOH (1g/kg i.p.) elicited a reduction in the stimulant effect induced by low doses of MDPV (0.1-0.3mg/kg, s.c.) in rats, jointly with a decrease in blood and brain MDPV concentrations. Experiments in rat liver microsomes showed different effects depending on the [MDPV]/[EtOH] relationship, evidencing, at certain concentrations, the enhancing effect of EtOH on MDPV metabolism. These suggest that EtOH interacts with MDPV at microsomal level, increasing its metabolic rate. The interaction between both substances was also supported by results in plasma EtOH concentration, which were significantly increased by MDPV, in such a manner that EtOH elimination rate was significantly reduced. The possible toxicological impact of this phenomenon deserves further investigation. In contrast, the rewarding properties of MDPV were unaltered by EtOH. Microdialysis experiments verified that, in the NAcc, both substances could also act synergistically, in such a manner that extracellular dopamine concentrations are maintained. Finally, if the psychostimulant effect induced by MDPV decreased with EtOH, it could favor the boosting and re-dosing in search of the desired effects. However, as the rewarding effect of each dose of the substance would not decrease, the addictive liability could increase considerably. Moreover, we must warn about the increase in EtOH concentrations when consumed concomitantly with MDPV.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section, University of Barcelona, Barcelona, Spain; Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: López-Arnau
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section, University of Barcelona, Barcelona, Spain; Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; Department of Psychology, Faculty of Psychology, University Enrique Díaz de León, Guadalajara, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Buenrostro-Jáuregui
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section, University of Barcelona, Barcelona, Spain; Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Muñoz-Villegas
authors.affiliation: Integrative Pharmacology and Systems Neuroscience, IMIM (Hospital del Mar Research Institute), Barcelona, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rodríguez-Morató
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section, University of Barcelona, Barcelona, Spain; Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ciudad-Roberts
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section, University of Barcelona, Barcelona, Spain; Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Duart
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section, University of Barcelona, Barcelona, Spain; Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Camarasa
authors.affiliation: Integrative Pharmacology and Systems Neuroscience, IMIM (Hospital del Mar Research Institute), Barcelona, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain; Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto Salud Carlos III, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: De la Torre
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section, University of Barcelona, Barcelona, Spain; Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain. Electronic address: d.pubill@ub.edu.
authors.forename: D
authors.initials: D
authors.lastname: Pubill
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section, University of Barcelona, Barcelona, Spain; Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Escubedo
mesh_terms: D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D052117:Benzodioxoles / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects*; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000094982:Synthetic Cathinone
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D000697:Central Nervous System Stimulants; D011759:Pyrrolidines; D000431:Ethanol; C023665:cathinone; D000094982:Synthetic Cathinone
keywords: 3,4-Methylenedioxypyrovalerone; Conditioning; Ethanol; Interaction; Psychostimulant