Selective Deficits in Contingency-Driven Ethanol Seeking Following Chronic Ethanol Exposure in Male Mice.

Abstract

People with alcohol use disorders exhibit an overreliance on habitual response strategies which may result from a history of chronic alcohol exposure. Although habits are defined by behavior that persists despite changes in outcome value and in action-outcome relationships, most research investigating the effects of ethanol exposure on habits has focused only on outcome devaluation. A clear understanding of the effects of chronic alcohol exposure on the ability to flexibly update behavior may provide insight into the behavioral deficits that characterize alcohol use disorders. To dissociate the effects of chronic intermittent ethanol (CIE) exposure on contingency-mediated sucrose versus ethanol seeking, adult male C57Bl/6J mice were assigned to 2 separate experiments. In the first experiment, mice were trained to self-administer ethanol prior to 2 cycles of interleaved CIE exposure by vapor inhalation. In a second experiment, mice were trained to self-administer sucrose and ethanol in separate training sessions prior to 4 cycles of interleaved CIE. The use of contingencies to mediate reward seeking was assessed using a contingency degradation paradigm. In mice trained to self-administer only ethanol, 2weeks of CIE resulted in escalated self-administration. At this time point, CIE-exposed mice, but not air-exposed controls, exhibited ethanol seeking that was insensitive to changes in action-outcome contingency, consistent with habitual ethanol seeking. In mice trained to self-administer ethanol and sucrose rewards in sequential sessions, no escalation in self-administration across 4weeks of CIE was observed. Under these conditions, neither Air- nor CIE-exposed mice reduced ethanol seeking in response to contingency degradation. In contrast, sucrose seeking remained goal-directed. Our results suggest that chronic ethanol exposure impairs contingency-driven ethanol seeking more readily than sucrose-seeking behavior. Further, these findings indicate that the transition from contingency-mediated ethanol seeking occurs more rapidly than for sucrose seeking under similar ethanol exposure conditions.