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Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

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Abstract

Rationale

Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans.

Objectives

The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats.

Materials and methods

In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers.

Results

Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats.

Conclusions

The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.

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Acknowledgments

This work was supported by grant AA013860 to CLC from the National Institute on Alcohol Abuse and Alcoholism. Acamprosate was generously provided by Forest Research Institute, Jersey City, NJ. Dr. Hank Samson provided insight and discussion essential for the development of the behavioral paradigm.

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Authors and Affiliations

  1. Center for Alcohol and Addiction Studies, Brown University, Providence, RI, 02912, USA

    Cristine L. Czachowski & Michael J. DeLory

  2. Departments of Psychology and Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN, 46202, USA

    Cristine L. Czachowski

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  1. Cristine L. Czachowski
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  2. Michael J. DeLory
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Correspondence to Cristine L. Czachowski.

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Czachowski, C.L., DeLory, M.J. Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats. Psychopharmacology 204, 335–348 (2009). https://doi.org/10.1007/s00213-009-1465-z

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  • DOI: https://doi.org/10.1007/s00213-009-1465-z

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