Effects of Ethanol Exposure on Subsequent Acquisition and Extinction of Ethanol Self-Administration and Expression of Alcohol-Seeking Behavior in Adult Alcohol-Preferring (P) Rats: I. Periadolescent Exposure

Authors

  • Zachary A. Rodd-Henricks,

    Corresponding author
    1. Department of Psychiatry, Institute of Psychiatric Research (ZAR-H, RLB, KAK, JMM, WJM) and the Departments of Medicine (LL, T-KL) and Biochemistry (WJM, LL, T-KL), Indiana University School of Medicine, Indianapolis, Indiana; VA Medical Center (LL), Indianapolis; and the Department of Psychology (JMM), Purdue School of Science, Indiana University-Purdue University at Indianapolis.
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  • Richard L. Bell,

    1. Department of Psychiatry, Institute of Psychiatric Research (ZAR-H, RLB, KAK, JMM, WJM) and the Departments of Medicine (LL, T-KL) and Biochemistry (WJM, LL, T-KL), Indiana University School of Medicine, Indianapolis, Indiana; VA Medical Center (LL), Indianapolis; and the Department of Psychology (JMM), Purdue School of Science, Indiana University-Purdue University at Indianapolis.
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  • Kelly A. Kuc,

    1. Department of Psychiatry, Institute of Psychiatric Research (ZAR-H, RLB, KAK, JMM, WJM) and the Departments of Medicine (LL, T-KL) and Biochemistry (WJM, LL, T-KL), Indiana University School of Medicine, Indianapolis, Indiana; VA Medical Center (LL), Indianapolis; and the Department of Psychology (JMM), Purdue School of Science, Indiana University-Purdue University at Indianapolis.
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  • James M. Murphy,

    1. Department of Psychiatry, Institute of Psychiatric Research (ZAR-H, RLB, KAK, JMM, WJM) and the Departments of Medicine (LL, T-KL) and Biochemistry (WJM, LL, T-KL), Indiana University School of Medicine, Indianapolis, Indiana; VA Medical Center (LL), Indianapolis; and the Department of Psychology (JMM), Purdue School of Science, Indiana University-Purdue University at Indianapolis.
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  • William J. McBride,

    1. Department of Psychiatry, Institute of Psychiatric Research (ZAR-H, RLB, KAK, JMM, WJM) and the Departments of Medicine (LL, T-KL) and Biochemistry (WJM, LL, T-KL), Indiana University School of Medicine, Indianapolis, Indiana; VA Medical Center (LL), Indianapolis; and the Department of Psychology (JMM), Purdue School of Science, Indiana University-Purdue University at Indianapolis.
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  • Lawrence Lumeng,

    1. Department of Psychiatry, Institute of Psychiatric Research (ZAR-H, RLB, KAK, JMM, WJM) and the Departments of Medicine (LL, T-KL) and Biochemistry (WJM, LL, T-KL), Indiana University School of Medicine, Indianapolis, Indiana; VA Medical Center (LL), Indianapolis; and the Department of Psychology (JMM), Purdue School of Science, Indiana University-Purdue University at Indianapolis.
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  • Ting-Kai Li

    1. Department of Psychiatry, Institute of Psychiatric Research (ZAR-H, RLB, KAK, JMM, WJM) and the Departments of Medicine (LL, T-KL) and Biochemistry (WJM, LL, T-KL), Indiana University School of Medicine, Indianapolis, Indiana; VA Medical Center (LL), Indianapolis; and the Department of Psychology (JMM), Purdue School of Science, Indiana University-Purdue University at Indianapolis.
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  • This study was supported in part by NIAAA Grants AA07462, AA07611, AA10256, and AA11261.

Zachary A. Rodd-Henricks, PhD, Indiana University School of Medicine, Institute of Psychiatric Research, 791 Union Dr., Indianapolis, IN 46202–4887; Fax: 317–274–1365; E-mail: zrodd@iupui.edu.

Abstract

Background The current study examined the effects of ethanol (EtOH) drinking during periadolescence on the subsequent acquisition and extinction of operant self-administration of EtOH and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats to test the hypothesis that alcohol drinking during periadolescence produces enduring alterations that enhance the reinforcing properties of EtOH.

Methods Periadolescent female P rats were given 24 hr free-choice access to 15% (v/v) EtOH starting at postnatal day (PND) 30 and ending on PND 60 or were similarly housed and received water only. On PND 75, without any prior training, periadolescent alcohol-drinking and periadolescent alcohol-naïve rats were placed in standard two-lever (15% EtOH and water) chambers to examine acquisition of EtOH self-administration with a fixed ratio (FR) 1 schedule of reinforcement. After the acquisition phase and after stable responding was established on an FR5 for EtOH and FR1 for water, P rats underwent extinction training for both EtOH and water rewards. After extinction training and a 2 week home cage period, rats were returned to the operant chambers in the absence of reward for seven consecutive sessions (Pavlovian spontaneous recovery). After this testing period, animals were maintained in their home cage for a week before being returned to the operant chambers and allowed to respond for EtOH and water (reacquisition).

Results Compared with periadolescent alcohol-naïve rats, periadolescent alcohol-drinking rats acquired EtOH responding sooner (i.e., in the first acquisition session), displayed a greater resistance to extinguish EtOH responding (i.e., higher levels of responding in sessions 4–6), had higher responding for more sessions on the EtOH lever in the absence of reward after a prolonged home cage rest period, and had a more prolonged elevated level of EtOH responding during reacquisition (four sessions versus one session).

Conclusions Overall, the results suggest that periadolescent EtOH drinking by P rats produced long-lasting alterations in the reinforcing effects of alcohol, which increased the likelihood that alcohol drinking would be initiated in adulthood, decreased the likelihood that once adult alcohol drinking began it could be extinguished easily, and increased the potential for relapse.

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