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Effects of acute withdrawal on ethanol-induced conditioned place preference in DBA/2J mice

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Abstract

Rationale

Reexposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol.

Objective

The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal.

Methods

DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0, or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS−). The withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The no-withdrawal (NW) group did not experience acute withdrawal during conditioning trials but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal.

Results

All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity.

Conclusions

Acute withdrawal enhanced ethanol’s rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism.

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Acknowledgments

Research reported in this paper was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award numbers R01AA007702, R01AA020866, and T32AA007468. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Thanks are extended to Nancy Bormann for her preliminary work on this topic and her help in developing an earlier version of the experimental design and procedure used here. We also thank Melanie Pina for her comments on an earlier draft of the paper. Experiments reported here comply with the current laws of the USA.

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Authors and Affiliations

  1. Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, Portland, OR, 97239-3098, USA

    Sarah E. Dreumont & Christopher L. Cunningham

  2. Department of Behavioral Neuroscience L470, School of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA

    Christopher L. Cunningham

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  1. Sarah E. Dreumont
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  2. Christopher L. Cunningham
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Correspondence to Christopher L. Cunningham.

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Dreumont, S.E., Cunningham, C.L. Effects of acute withdrawal on ethanol-induced conditioned place preference in DBA/2J mice. Psychopharmacology 231, 777–785 (2014). https://doi.org/10.1007/s00213-013-3291-6

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  • DOI: https://doi.org/10.1007/s00213-013-3291-6

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