Effects of Repeated Alcohol Deprivations on Operant Ethanol Self-Administration by Alcohol-Preferring (P) Rats

Abstract

We reported that repeated alcohol deprivations prolonged the expression of an alcohol-deprivation effect (ADE) under 24-h freechoice alcohol-drinking access and that the duration of the initial deprivation period had a positive effect of prolonging the duration of the ADE. 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 alcohol-preferring (P) rats to test the hypothesis that repeated deprivations can increase the reinforcing effects of ethanol (ETOH). Adult male P rats were trained in two-lever operant chambers to self-administer 15% ETOH (v/v) on a fixed-ratio 5 (FR-5) and water on a FR-1 schedule of reinforcement in daily 1-h sessions. Following 6 weeks of daily 1-h sessions, the P rats were randomly assigned to one of four groups (n ¼ 10/group): nondeprived or deprived of alcohol for 2, 5, or 8 weeks. Following this initial period, the deprived groups were given 15% ETOH 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 fourth deprivation, the rats underwent a progressive ratio test to determine the breakpoints (FR values) for the nondeprived and the deprived groups. Repeated deprivations increased both the magnitude and duration of the ADE as indicated by increased responding on the ETOH lever. However, the length of the initial deprivation had little effect on expression of the ADE except following the first deprivation, where an ADE was not observed for the 8-week group. Breakpoint values for responding on the ETOH lever for all three deprived groups were two-fold higher than the value for the nondeprived group. The results suggest that repeated cycles of alcohol deprivation and alcohol access increased the reinforcing effects of ETOH in the P rats.

Nucleus accumbens AGS3 expression drives ethanol seeking through Gβγ

“…EtOH abstinence did not alter AGS3 expression in several other forebrain nuclei related to motivated, goal-directed behavior (Table S1), indicating relatively specific regulation of AGS3 expression in the NAcore during EtOH abstinence. Like the EtOH deprivation effect (2,(6)(7)(8)(9), the increase in NAcore AGS3 expression was apparent after several weeks but not after 24 h of abstinence. Thus, increased NAcore AGS3 expression may represent a neural substrate of the enhanced motivation to seek EtOH during protracted abstinence.…”

“…ref. 8). Interestingly, several studies noted that repeated periods of drinking and abstinence in rodents can be necessary for, or at least increase the magnitude and persistence of, enhanced EtOH intake after deprivation (8,29,37).…”

“…Accordingly, there is considerable interest in neuroadaptations that develop during periods of abstinence that may promote drug seeking and relapse (3). Enhanced EtOH seeking during abstinence is observed in heavy social drinkers (4), non-human primates (5), and rodents (2,(6)(7)(8)(9), where this EtOH deprivation effect is hypothesized to model many aspects of compulsive EtOH seeking and consumption (refs. 2, 6, 8, but see ref.…”

Effects of alcohol and saccharin deprivations on concurrent ethanol and saccharin operant self-administration by alcohol-preferring (P) rats

“…In these rats, repeated cycles of alcohol availability and deprivation prolonged the expression of an ADE (Rodd et al, 2003;Rodd-Henricks et al, 2000a, 2000b. Exposure to repeated cycles of EtOH access and deprivation increases the breakpoint obtained for EtOH during a progressive ratio test (Rodd et al, 2003) and reduced the concentration of EtOH required to support self-administration directly into the posterior ventral tegmental area (Rodd et al, 2005).…”

“…The ADE has been used as model of alcohol craving to study the efficacy of drugs designed to prevent relapse drinking (Heyser et al, 1998;Kornet et al, 1991;Rodd et al, 2003Rodd et al, , 2004Rodd et al, , 2006Sinclair and Li, 1989;Spanagel and Zieglgansberger, 1997;Vengeliene et al, 2005).…”