title: Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood.
abstract: 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with powerful psychostimulant effects. It selectively inhibits the dopamine transporter (DAT) and is 10-50-fold more potent as a DAT blocker than cocaine, suggesting a high abuse liability. The main objective of the present study was to assess the consequences of an early (adolescence) MDPV exposure on the psychostimulant, rewarding and reinforcing effects induced by cocaine in adult mice.
  
  
  
  Twenty-one days after MDPV pretreatment (1.5 mg·kg-1, s.c., twice daily for 7 days), adult mice were tested with cocaine, using locomotor activity, conditioned place preference and self-administration (SA) paradigms. In parallel, dopamine D2receptor density and the expression of c-Fos and ΔFosB in the striatum were determined.
  
  
  
  MDPV treatment enhanced the psychostimulant and conditioning effects of cocaine. Acquisition of cocaine SA was unchanged in mice pretreated with MDPV, whereas the breaking point achieved under a progressive ratio programme and reinstatement after extinction were higher in this group of mice. MDPV decreased D2receptor density but increased ΔFosB expression three-fold. As expected, acute cocaine increased c-Fos expression, but MDPV pretreatment negatively influenced its expression. ΔFosB accumulation declined during MDPV withdrawal, although it remained elevated in adult mice when tested for cocaine effects.
  
  
  
  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.
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: R
authors.initials: R
authors.lastname: López-Arnau
authors.affiliation: Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Luján
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: L
authors.initials: L
authors.lastname: Duart-Castells
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: D
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.
authors.forename: J
authors.initials: J
authors.lastname: Camarasa
authors.affiliation: Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.|Neuroscience Research Programme, IMIM-Hospital del Mar Research Institute, Barcelona, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Valverde
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: E
authors.initials: E
authors.lastname: Escubedo
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration; D000094982:Synthetic Cathinone
chemical_list: D052117:Benzodioxoles; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D003042:Cocaine; D000094982:Synthetic Cathinone