Effects of multiple alcohol deprivations on operant ethanol self-administration by high-alcohol-drinking replicate rat lines Scott M. Oster a , Jamie E. Toalston a , Kelly A. Kuc b , Tylene J. Pommer b , James M. Murphy a,b , Lawrence Lumeng c , Richard L. Bell b , William J. McBride b,d , Zachary A. Rodd b, * a Department of Psychology, Purdue School of Science, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, USA b Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA c Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA d Department of Biochemistry, Indiana University School of Medicine, Indianapolis, IN 46202, USA Received 8 March 2006; received in revised form 1 June 2006; accepted 1 June 2006 Abstract Previously, we reported that the expression of an alcohol deprivation effect (ADE) under 24-h free-choice alcohol-drinking access in high-alcohol-drinking (HAD) replicate lines of rats is dependent upon repeated cycles of alcohol access and forced abstinence. In the pres- ent study, operant techniques (including progressive ratio measures) were used to examine the effects of initial deprivation length and num- ber of deprivation cycles on the magnitude and duration of the ADE in HAD rats to test the hypothesis that repeated deprivations increase the reinforcing effects of ethanol. Adult male HAD-1 and HAD-2 rats were trained in two-lever operant chambers to concurrently self- administer 15% ethanol (v/v) on a fixed-ratio (FR)-5 schedule and water on an FR-1 schedule of reinforcement in daily 1-h sessions. Following 10 weeks of daily 1-h sessions, the HAD-1 and HAD-2 rats were randomly assigned to one of four groups (n 5 6e8/group/line): nondeprived, or deprived of alcohol for 2, 5, or 8 weeks. Following this initial period, the deprived groups were given 15% ethanol again in the operant chambers for a 2-week period, following which they were deprived again for 2 weeks (all three deprived groups). Following the fifth deprivation, the rats underwent a progressive ratio test to determine the breakpoints for the nondeprived and deprived groups. The expression of an ADE under operant conditions in HAD rats was dependent upon exposure to repeated cycles of ethanol access and abstinence. Additionally, repeated deprivations increased both the magnitude and the duration of the ADE as indicated by increased responding on the ethanol lever for more sessions. Breakpoint values for the deprived groups were 1.5-fold and twofold higher than the value for the nondeprived group for the HAD-1 and HAD-2 rats, respectively. The results suggest that repeated alcohol deprivations increased the expression of an ADE and the reinforcing effects of ethanol in both HAD replicate lines of rats, and these effects were more pronounced in the HAD-2 line than the HAD-1 line. Ó 2006 Elsevier Inc. All rights reserved. Keywords: Alcohol deprivation effect; Operant self-administration; High-alcohol-drinking rats; Repeated deprivations; Progressive ratio 1. Introduction The alcohol deprivation effect (ADE) is defined as a tem- porary increase in the voluntary intake of ethanol solutions and the ratio of ethanol to total fluid intake over baseline drinking conditions, when ethanol is reinstated following a period of alcohol deprivation (Sinclair & Senter, 1967, 1968). The ADE has been hypothesized to be an animal model of alcohol craving (Heyser et al., 1997; Sinclair & Li, 1989) and has been used to examine the efficacy of pharmacological agents to prevent relapse drinking (Heyser et al., 1998; Kornet et al., 1991; Spanagel & Zieglgansberger, 1997). The ADE phenomenon has been studied in several lines of rats. Alcohol-preferring (P) rats given continuous access to free-choice ethanol for approximately 1 month demon- strated an ADE after intervals of 12 h or 1 week (Sinclair & Li, 1989). In addition, with daily 4-h operant scheduled access sessions, P rats exhibited an increase in responding for ethanol compared to baseline after 2 weeks of alcohol deprivation (McKinzie et al., 1998). In contrast, other rat lines that were selectively bred for high alcohol consump- tion did not exhibit an ADE after the initial deprivation fol- lowing 24-h free-choice drinking conditions. The Alko This study was supported in part by NIAAA grants AA07611, AA10721, and AA11261. * Corresponding author. Tel.: þ1-317-278-3003; fax: þ1-317-274- 1365. E-mail address: zrodd@iupui.edu (Z.A. Rodd). 0741-8329/06/$ e see front matter Ó 2006 Elsevier Inc. All rights reserved. doi: 10.1016/j.alcohol.2006.06.001 Alcohol 38 (2006) 155e164