title: Alcohol enhances the psychostimulant and conditioning effects of mephedrone in adolescent mice; postulation of unique roles of D3 receptors and BDNF in place preference acquisition.
abstract: OBJECTIVE
  The psychostimulant mephedrone is often consumed in combination with alcohol (EtOH). This kind of drug consumption during adolescence is a matter of concern.
  
  
  METHODS
  We studied, in adolescent CD-1 mice, whether EtOH could enhance the psychostimulant (locomotor acivity) and rewarding [conditioned place preference (CPP)] effects of mephedrone. We also determined the transcriptional changes associated with a conditioning treatment with these drugs.
  
  
  RESULTS
  Mephedrone (10 mg·kg(-1)) increased locomotor activity, which was further enhanced by 40% when combined with EtOH (1 g·kg(-1)). This enhancement was blocked by haloperidol. Furthermore, mephedrone (25 mg·kg(-1)) induced CPP, which increased by 70% when administered with a dose of EtOH that was not conditioning by itself (0.75 g·kg(-1)). There was enhanced expression of the D3 dopamine receptor mRNA (Drd3) and Arpc5 in all drug-treated groups. The D3 receptor antagonist SB-277011A and the BDNF receptor antagonist ANA-12 completely prevented CPP as well as the increases in Drd3 in all groups. Accordingly, increased expression of BDNF mRNA in medial prefrontal cortex was detected at 2 and 4 h after mephedrone administration.
  
  
  CONCLUSIONS
  If translated to humans, the enhancement of mephedrone effects by ethanol could result in increased abuse liability. D3 receptors and BDNF play a key role in the establishment of CPP by mephedrone, although an accompanying increase in other synaptic plasticity-related genes may also be necessary.
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Ciudad-Roberts
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Camarasa
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Biomedicine (IBUB), Faculty of Pharmacy, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Ciudad
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy, Universitat de Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Pubill
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Escubedo
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D020869:Gene Expression Profiling; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D050637:Receptors, Dopamine D3 / Q000235:genetics / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D050637:Receptors, Dopamine D3; D000431:Ethanol; D008694:Methamphetamine; C548233:mephedrone