Loss of Flexibility in Alcohol-Taking Rats: Promoting Factors

Abstract

Alcohol consumption in humans can move from a flexible pattern of intake to an inflexible (addictive) one. Several endogenous and exogenous factors are discussed to be involved in this transition. The purpose of this study was to examine factors that might promote the development of inflexibility. Over a period of 52 weeks (long-term) rats had continuously free choice between differently concentrated alcohol solutions and tap water (four-bottle paradigm). After 4 months of alcohol deprivation, a retest with free choice of alcohol was performed. Bitter-taste conditions were used to test the flexibility of alcohol taking. In the retest alcohol-experienced rats revealed a much higher alcohol intake than previously alcohol-naive ones. Part of the alcohol-experienced animals showed impairment of flexibility in alcohol taking. During long-term choice, some groups were submitted to experimental interventions that might affect addiction development (stress, withdrawal, limited access, adverse consequences). Rats with limited access to alcohol at the end of the long-term choice period took more alcohol and were less flexible in the retest than any other group. It is suggested that an unsatisfied urge for alcohol leads to impairment of control over alcohol drinking.

Nucleus accumbens AGS3 expression drives ethanol seeking through Gβγ

“…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). Our model using an outbred rat strain yielded a significant increase in EtOH-seeking behavior after a single deprivation (Fig.…”

“…2 A) and continued EtOH seeking in the absence of EtOH delivery but in the presence of EtOH-associated cues (Fig. 2 E and F) suggest that the increased EtOH-seeking motivation modeled here may represent uncontrolled, compulsive responding (2,29). Because NAcore AGS3 expression increased during abstinence from repeated EtOH (Fig.…”

“…9). Thus, these data suggest that enhanced motivation to seek EtOH during abstinence may represent some aspects of human alcoholic, compulsive behavior (1,2,29). In addition, the enhanced willingness to work for EtOH was dose-dependently reduced by naltrexone (Fig.…”

“…Enhanced motivation was due to increased control of behavior by EtOH-predictive cues because responding persisted even when the EtOH reinforcer was not delivered (Fig. 2 E and F) and may therefore reflect uncontrolled or compulsive behavior (2,29). Importantly, the enhanced EtOH seeking during abstinence was dramatically normalized by AGS3 knockdown (Fig.…”

“…An important aspect of the present study was the use of a PR to assess motivational changes, because many reports have examined EtOH consumption, which does not delineate motivation per se (2,29). Thus, these results, in combination with continued cue-driven seeking in the absence of reinforcer attainment (Fig.…”