Ethanol drinking-in-the-dark facilitates behavioral sensitization to ethanol in C57BL/6J, BALB/cByJ, but not in mu-opioid receptor deficient CXBK mice

摘要

Background: Neuroplasticity associated with drug-induced behavioral sensitization has been associated withexcessive drug pursuit and consumption characteristic of addiction. Repeated intraperitoneal (ip) injectionsof ethanol (EtOH) can induce psychomotor sensitization in mice. In terms of its clinical relevance, however, itis 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 ofEtOH drinking in mice; EtOH replaces water for 2 or 4 h, starting 3 h after the beginning of the dark cycle.Animals followed a 3-week DID protocol prior to an evaluation of EtOH-induced locomotor activity (acute andrepeated EtOH). For the first week, animals had access to 20% EtOH. On weeks 2 and 3, different concentrationsof 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 brainmu-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. 3 g/kg in 2 h), that werehigher than those showed by BALB. All animals, regardless of genotype, adjusted volume of EtOH intake toobtain 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 ofmu-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-inducedneuroplasticity supporting psychomotor sensitization, a process that might require participation of muopioid receptors.