title: Ethanol drinking-in-the-dark facilitates behavioral sensitization to ethanol in C57BL/6J, BALB/cByJ, but not in mu-opioid receptor deficient CXBK mice.
abstract: BACKGROUND
  Neuroplasticity associated with drug-induced behavioral sensitization has been associated with excessive drug pursuit and consumption characteristic of addiction. Repeated intraperitoneal (ip) injections of ethanol (EtOH) can induce psychomotor sensitization in mice. In terms of its clinical relevance, however, it is important to determine whether this phenomenon can also be produced by voluntary EtOH consumption.
  
  
  METHODS
  The present investigation used a drinking-in-the-dark (DID) methodology to induce high levels of EtOH drinking in mice; EtOH replaces water for 2 or 4h, starting 3h after the beginning of the dark cycle. Animals followed a 3-week DID protocol prior to an evaluation of EtOH-induced locomotor activity (acute and repeated EtOH). For the first week, animals had access to 20% EtOH. On weeks 2 and 3, different concentrations of EtOH (10, 20 or 30%) were used. Three different inbred strains of mice were used: C57BL/6J (B6), BALB/cByJ (BALB), and CXBK. The CXBK mouse line was used because of its reduced expression and functioning of brain mu-opioid receptors, which have been suggested to participate in the development of EtOH-induced sensitization. B6 and BALB mice were used as controls.
  
  
  RESULTS
  B6 and CXBK mice presented comparable levels of EtOH drinking (approx. 3g/kg in 2h), that were higher than those showed by BALB. All animals, regardless of genotype, adjusted volume of EtOH intake to obtain stable g/kg of EtOH across concentrations. Previous EtOH DID produced (B6) or potentiated (BALB) sensitization to EtOH; this effect was not seen in CXBK. Western blot analysis showed a reduced number of mu-opioid receptors in several brain regions of CXBK as compared to that of B6 and BALB mice.
  
  
  CONCLUSIONS
  In summary, here we show that the DID methodology can be used to trigger EtOH-induced neuroplasticity supporting psychomotor sensitization, a process that might require participation of mu-opioid receptors.
authors.affiliation: Area de Psicobiología, Universitat Jaume I, Av. Sos Baynat s/n, 12071, Castellón, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Tarragón
authors.forename: Pablo
authors.initials: P
authors.lastname: Baliño
authors.forename: Carlos M G
authors.initials: CM
authors.lastname: Aragon
authors.forename: Raúl
authors.initials: R
authors.lastname: Pastor
mesh_terms: D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003624:Darkness; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity
chemical_list: D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D000431:Ethanol; D009271:Naltrexone