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

Alcohol Clin Exp Res. 2020 Sep;44(9):1896-1905. doi: 10.1111/acer.14418. Epub 2020 Aug 20.

Abstract

Background: 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.

Methods: 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.

Results: In mice trained to self-administer only ethanol, 2 weeks 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 4 weeks 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.

Conclusions: 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.

Keywords: Chronic intermittent ethanol; Contingency; Degradation; Goal-directed behavior; Habit; Self-administration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Alcoholism / physiopathology*
  • Animals
  • Behavior, Animal*
  • Central Nervous System Depressants / administration & dosage*
  • Disease Models, Animal
  • Drug-Seeking Behavior*
  • Ethanol / administration & dosage*
  • Male
  • Mice
  • Reward*
  • Self Administration
  • Sucrose / administration & dosage
  • Sweetening Agents / administration & dosage

Substances

  • Central Nervous System Depressants
  • Sweetening Agents
  • Ethanol
  • Sucrose