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

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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.


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 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 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.


B6 and CXBK mice presented comparable levels of EtOH drinking (approx. 3 g/kg in 2 h), 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.


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.


▸ Elevated ethanol drinking facilitates ethanol-induced psychomotor sensitization. ▸ Mu-opiod receptor deficiency prevents drinking-mediated sensitization to ethanol. ▸ Drinking-in-the-Dark tests can be used to study ethanol-induced neuroplasticity.

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