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The effects of repeated corticosterone exposure on the interoceptive effects of alcohol in rats

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Abstract

Rationale and objective

Repeated and/or heightened elevations in glucocorticoids (e.g., repeated stress) can promote escalated drug-taking behaviors and induce compromised HPA axis function. Given that interoceptive/subjective drug cues are a fundamental factor in drug-taking behavior, we sought to determine the effects of exposure to repeated elevations in the glucocorticoid corticosterone (CORT) on the interoceptive effects of alcohol in rats using drug discrimination techniques.

Methods

Male Long Evans rats trained to discriminate alcohol (1 g/kg, IG) vs. water were exposed to CORT (300 μg/ml) in the home cage drinking water for 7 days. The interoceptive effects of experimenter- and self-administered alcohol were assessed and HPA axis function was determined.

Results

The interoceptive effects of experimenter- and self-administered alcohol were blunted following CORT. Control experiments determined that this decreased sensitivity was unrelated to discrimination performance impairments or decreased CORT levels at the time of testing and was dependent on repeated CORT exposure. Susceptibility to compromised HPA axis function following CORT exposure was suggested by an altered pattern of CORT secretion and blunted CORT response following injection of the synthetic glucocorticoid dexamethasone.

Conclusions

These findings present a possible behavioral mechanism for escalated alcohol drinking during episodes of heightened elevations in glucocorticoids (e.g., stress). That is, during these episodes, individuals may consume more alcohol to achieve the desired interoceptive effects. Understanding these behavioral mechanisms may lead to a better understanding of factors that promote alcoholism and alcohol abuse in at risk populations.

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Acknowledgments

The authors would like to thank Dr. Cynthia Kuhn for discussions on corticosterone data interpretation, and Drs. Sarah Holstein and Sara Faccidomo, and Kelly Psilos for help with blood collection and/or blood analyses. This work was supported in part by funds from the National Institutes of Health AA016009 (JB), AA019682 (JB), AA014983 (CWH), ABMRF/The Foundation for Alcohol Research (JB), and by the Bowles Center for Alcohol Studies.

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Authors and Affiliations

  1. Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building, CB#7178, Chapel Hill, NC, 27599, USA

    Joyce Besheer, Kristen R. Fisher, Julie J. M. Grondin, Reginald Cannady & Clyde W. Hodge

  2. Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Joyce Besheer, Reginald Cannady & Clyde W. Hodge

  3. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Joyce Besheer & Clyde W. Hodge

  4. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Clyde W. Hodge

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  1. Joyce Besheer
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  2. Kristen R. Fisher
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  3. Julie J. M. Grondin
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  4. Reginald Cannady
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  5. Clyde W. Hodge
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Correspondence to Joyce Besheer.

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Besheer, J., Fisher, K.R., Grondin, J.J.M. et al. The effects of repeated corticosterone exposure on the interoceptive effects of alcohol in rats. Psychopharmacology 220, 809–822 (2012). https://doi.org/10.1007/s00213-011-2533-8

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