Voluntary ethanol drinking in C57BL/6J and DBA/2J mice before and after sensitization to the locomotor stimulant effects of ethanol

Rationale: Drug-induced sensitization has been associated with enhanced drug self-administration and may contribute to drug addiction. Objectives: We investigated the possible association between sensitization to the locomotor stimulant effects of ethanol (EtOH) and voluntary EtOH consumption. Methods: Mice of the EtOH-avoiding DBA/2J (D2) and EtOH-preferring C57BL/6J (B6) inbred strains were offered the choice of an EtOH solution versus tap water (EtOH-experienced) or just water (Naïve), and voluntary consumption was measured. Mice from each condition then received repeated EtOH or saline injections, and locomotor responses were measured. Subsequently, all mice were offered the choice of EtOH versus water, and voluntary consumption was again measured. A subsequent study examined relative susceptibility of D2 and B6 mice to EtOH-induced locomotor sensitization. Results: Voluntary EtOH consumption induced locomotor sensitization to an EtOH challenge in B6 mice. D2 mice consumed little EtOH, but developed sensitization with repeated EtOH treatments as expected. EtOH consumption was not altered in EtOH-sensitized D2 mice. Unexpectedly, B6 mice developed significant sensitization, and following sensitization, the EtOH-experienced EtOH-sensitized group consumed more EtOH than their EtOH-experienced saline-treated (non-sensitized) counterparts. In an independent study, B6 mice required between three and five EtOH injections to express sensitization, whereas for D2 mice, between one and three EtOH exposures were sufficient. Conclusions: Development of sensitization to the locomotor stimulant effects of EtOH may be associated with increased EtOH consumption in mice with high initial avidity for EtOH. In the same mice, voluntary EtOH consumption can also produce behavioral sensitization to the effects of EtOH.