Repeated cycles of chronic intermittent ethanol exposure in mice increases voluntary ethanol drinking and ethanol concentrations in the nucleus accumbens

This study examined the relationship between voluntary ethanol consumption and ethanol concentrations measured in the nucleus accumbens of ethanol dependent and nondependent C57BL/6J mice. Mice were offered ethanol in a two-bottle choice; limited access paradigm and consummatory behavior was monitored with lickometers. After baseline intake stabilized, mice received chronic intermittent ethanol (EtOH group) or air (CTL group) exposure by inhalation (16 h/day for 4 days) and then resumed drinking. Brain ethanol levels during voluntary drinking were measured by microdialysis procedures and compared to brain ethanol concentrations produced during chronic intermittent ethanol vapor exposure. Voluntary ethanol consumption progressively increased over repeated cycles of chronic intermittent ethanol exposure but remained unchanged in CTL mice. Analysis of lick patterns indicated EtOH mice consumed ethanol at a faster rate compared to CTL mice. The greater and faster rate of ethanol intake in EtOH mice produced higher peak brain ethanol concentrations compared to CTL mice, and these levels were similar to levels produced during chronic intermittent ethanol exposure. These results show that in this model of dependence and relapse drinking, dependent mice exhibit enhanced voluntary ethanol consumption relative to nondependent controls, which consequently produces blood and brain ethanol concentrations similar to those experienced during chronic intermittent ethanol exposure.