title: Changes in CREB and deltaFosB are associated with the behavioural sensitization induced by methylenedioxypyrovalerone.
abstract: Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone which has recently emerged as a designer drug of abuse. The objective of this study was to investigate the locomotor sensitization induced by MDPV in adolescent mice, and associated neuroplastic changes in the nucleus accumbens and striatum through deltaFosB and CREB expression. Behavioural testing consisted of three phases: Phase I: conditioning regimen with MDPV (0.3 mg/kg/day for five days) or saline; Phase II: resting (11 days); Phase III: challenged with MDPV (0.3 mg/kg), cocaine (10 mg/kg) or saline on day 16 for both groups. Mice repeatedly exposed to MDPV increased locomotor activity by 165-200% following acute MDPV or cocaine administration after an 11-day resting period, showing a MDPV-induced sensitization to itself and to cocaine. An explanation for this phenomenon could be the common mechanism of action between these two psychostimulants. Furthermore, the MDPV challenge resulted in higher levels of phospho-CREB in MDPV-conditioned mice compared with MDPV-naive mice, probably due to an up-regulation of the cAMP pathway. Likewise, MDPV exposure induced a persistent increase in the striatal expression of deltaFosB; the priming dose of MDPV also produced a significant increase in the accumbal expression of this transcription factor. This study constitutes the first evidence that an exposure to a low dose of MDPV during adolescence induces behavioural sensitization and provides a neurobiological basis for a relationship between MDPV and cocaine. We hypothesize that, similar to cocaine, both CREB and deltaFosB play a role in the induction of this behavioural sensitization.
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain Department of Psychology, Faculty of Psychology, University Enrique Díaz de León, Guadalajara, México.
authors.forename: Mario
authors.initials: M
authors.lastname: Buenrostro-Jáuregui
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Andres
authors.initials: A
authors.lastname: Ciudad-Roberts
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz-Villegas
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: López-Arnau
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Pubill
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain eescubedo@ub.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Escubedo
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Camarasa
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D052117:Benzodioxoles / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015198:Designer Drugs / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000094982:Synthetic Cathinone
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D000697:Central Nervous System Stimulants; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D015198:Designer Drugs; C483819:Fosb protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D011759:Pyrrolidines; D014157:Transcription Factors; C023665:cathinone; D003042:Cocaine; D000094982:Synthetic Cathinone
keywords: CREB; MDPV; cocaine; deltaFosB; sensitization