Central Administration of an Opiate Antagonist Decreases Oral Ethanol Self-Administration in Rats

Authors

  • Charles J. Heyser,

    Corresponding author
    1. Department of Neuropharmacology (A.J.R., G.F.K.), The Scripps Research Institute, La Jolla, California; the Department of Anesthesiology (G.S.), UCSD School of Medicine, San Diego, California; and the Department of Psychology (C.J.H.), Franklin & Marshall College, Lancaster, Pennsylvania.
      Reprint requests: Charles J. Heyser, Ph.D., Department of Psychology, Franklin & Marshall College, P.O. Box 3003, Lancaster, PA 17604; Fax: 717-291-4387.
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  • Amanda J. Roberts,

    1. Department of Neuropharmacology (A.J.R., G.F.K.), The Scripps Research Institute, La Jolla, California; the Department of Anesthesiology (G.S.), UCSD School of Medicine, San Diego, California; and the Department of Psychology (C.J.H.), Franklin & Marshall College, Lancaster, Pennsylvania.
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  • Gery Schulteis,

    1. Department of Neuropharmacology (A.J.R., G.F.K.), The Scripps Research Institute, La Jolla, California; the Department of Anesthesiology (G.S.), UCSD School of Medicine, San Diego, California; and the Department of Psychology (C.J.H.), Franklin & Marshall College, Lancaster, Pennsylvania.
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  • George F. Koob

    1. Department of Neuropharmacology (A.J.R., G.F.K.), The Scripps Research Institute, La Jolla, California; the Department of Anesthesiology (G.S.), UCSD School of Medicine, San Diego, California; and the Department of Psychology (C.J.H.), Franklin & Marshall College, Lancaster, Pennsylvania.
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  • This study was supported in part by the National Institute on Alcohol Abuse and Alcoholism Grants AA08459, AA06420, andAA07456 (G.F.K.) and Grant F32 AA05403 (C.J.H.).

Reprint requests: Charles J. Heyser, Ph.D., Department of Psychology, Franklin & Marshall College, P.O. Box 3003, Lancaster, PA 17604; Fax: 717-291-4387.

Abstract

Background: Opioid peptides have been implicated in various behavioral actions of alcohol, including its reinforcing effects; however, the role of specific brain sites for these actions remains to be explored. The present study examined the effects of intracerebroventricular (ICV) or intracerebral injections of an opiate antagonist (methylnaloxonium) on ethanol self-administration. The nucleus accumbens and amygdala were selected as intracerebral sites because these regions have been implicated in the reinforcing effects of drugs of abuse.

Methods: Male Wistar rats were trained in a limited-access paradigm (30 min/day) to respond for ethanol (10% w/v) or water in a two-lever free-choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, animals were implanted stereotaxically with a guide cannula above the lateral ventricle or with bilateral guide cannulae either above the nucleus accumbens or amygdala. After postoperative recovery of stable baseline responding, the rats were tested 15 min after ICV or intracerebral microinjections of methylnaloxonium (0-2000 ng).

Results: Injections of methylnaloxonium into the amygdala significantly reduced responding for ethanol at doses of 250–500 ng. Injections of methylnaloxonium into the nucleus accumbens significantly reduced responding for ethanol at doses of 500–1000 ng, whereas higher doses were needed ICV.

Conclusions: These results provide evidence that opioid receptors located in the amygdala and nucleus accumbens may be involved in the regulation of ethanol self-administration.

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