Effects of multiple alcohol deprivations on operant ethanol self-administration by high-alcohol-drinking replicate rat lines

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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 present
study, operant techniques (including progressive ratio measures) were used to examine the effects of initial deprivation length and number
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 selfadminister
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 (n56e8/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. 2006 Elsevier Inc. All rights reserved.

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Effects of multiple alcohol deprivations on operant ethanol
self-administration by high-alcohol-drinking replicate rat lines
Scott M. Ostera, Jamie E. Toalstona, Kelly A. Kucb, Tylene J. Pommerb, James M. Murphya,b,
Lawrence Lumengc, Richard L. Bellb, William J. McBrideb,d, Zachary A. Roddb,*
aDepartment of Psychology, Purdue School of Science, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, USA
bDepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA
cDepartment of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
dDepartment 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 present
study, operant techniques (including progressive ratio measures) were used to examine the effects of initial deprivation length and number
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 selfadminister
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 (n56e8/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. 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 temporary
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 demonstrated
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 consumption
did not exhibit an ADE after the initial deprivation following
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 2006 Elsevier Inc. All rights reserved.
doi: 10.1016/j.alcohol.2006.06.001
Alcohol 38 (2006) 155e164

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