Effects of Chronic Ethanol Exposure on Oral Self-Administration of Ethanol or Saccharin by Wistar Rats

Authors

  • Gery Schulteis,

    Corresponding author
    1. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California.
      Reprint requests: Gery Schulteis, Ph.D., Department of Neuropharmacology, The Scripps Research Institute, 10666 North Torrey Pines Road, CVN 7, La Jolla, CA 92037.
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  • Petri Hyytiä,

    1. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California.
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  • Stephen C. Heinrichs,

    1. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California.
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  • George F. Koob

    1. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California.
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  • This research was supported in part by the National Institute on Alcohol Abuse and Alcoholism Grants AA08459 and AA06420 (to G.F.K). Two of the authors (G.S., S.C.H.) were supported by the National Institute on Alcohol Abuse and Alcoholism Training Grant AA07456 (to Floyd E. Bloom) and by a grant from the Alcoholic Beverage Medical Research Foundation (to G.F.K.).

Reprint requests: Gery Schulteis, Ph.D., Department of Neuropharmacology, The Scripps Research Institute, 10666 North Torrey Pines Road, CVN 7, La Jolla, CA 92037.

Abstract

The study of alcohol abuse traditionally has placed great emphasis on the development of tolerance and dependence as key factors. However, animal models of ethanol self-administration in dependent rats have been difficult to establish, caused in part by ethanol's aversive taste cues and subsequent aversive effects (i.e., “hangover” malaise) that prevent substantial ethanol consumption. In this study, this problem was addressed in animals trained to self-administer ethanol (10% w/v) in a sweetened-solution fading procedure before induction of dependence and repeated exposure to withdrawal. Once stable rates of responding for ethanol were achieved, a palatable liquid diet containing 8.7% (v/v) ethanol was introduced as the sole source of calories and fluid for one group of rats [ethanol diet (ED) group]. A second group of rats received a control diet with sucrose isocalorically substituted for ethanol (CD group). After 14–17 days of liquid diet exposure, the rats were withdrawn once a week for 4 weeks and 8 hr into each withdrawal session were allowed to self-administer ethanol or water for 60 min. As compared with CD rats, ED rats showed significantly greater intake of ethanol, but not water. No significant differences were found when separate groups of ED/CD rats were allowed to self-administer an alternate reinforcer (0.0075% saccharin solution). Rats who consistently had blood alcohol levels (BALs) above 100 mg% at the time of withdrawal sustained high levels of ethanol self-administration throughout the four withdrawal sessions. In contrast, rats who had an average BAL at withdrawal below 100 mg% showed progressive decreases in ethanol self-administration during repeated withdrawal episodes. The results demonstrated that chronic exposure to ethanol and repeated periods of abstinence are accompanied by elevated rates of ethanol intake in certain animals, and the persistence of elevated self-administration behavior of individual rats is predicted by their BAL at the time of withdrawal.

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