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Context-induced relapse to alcohol seeking after punishment in a rat model.

ABSTRACT: BACKGROUND:Rat studies have demonstrated that exposure to environments associated with alcohol intake reinstates alcohol seeking after extinction of alcohol-reinforced responding in a different context. However, extinction is limited as an abstinence model, because humans typically abstain because of negative consequences associated with excessive drinking. It is currently unknown whether alcohol-associated contexts can provoke relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences in a different context. METHODS:Alcohol-preferring P rats were first given home-cage access to 20% ethanol. Next, they were trained to self-administer 20% ethanol in one context (context A). Subsequently, all rats continued to self-administer alcohol in a different context (context B). For one group, 50% of alcohol-reinforced responses were punished by mild footshock; two other groups either received noncontingent shocks or no shock. A fourth group was given extinction training in context B. All rats were then tested for relapse to alcohol seeking under extinction conditions in contexts A and B. RESULTS:In Context B, alcohol-taking behavior was suppressed by contingent shock (punishment) and extinction training but not by noncontingent shock. In Context A, relapse to alcohol seeking was reliably observed in the punished and extinction groups; a context switch had no effect on alcohol seeking in the no-shock or noncontingent shock groups. CONCLUSIONS:Our data indicate that punishment-induced suppression of alcohol-taking behavior is context-dependent. We propose that our procedure can be used to explore mechanisms of context-induced relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences.

SUBMITTER: Marchant NJ

PROVIDER: S-EPMC3517691 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Context-induced relapse to alcohol seeking after punishment in a rat model.

Marchant Nathan J NJ Khuc Thi N TN Pickens Charles L CL Bonci Antonello A Shaham Yavin Y

Biological psychiatry 20120809 3

<h4>Background</h4>Rat studies have demonstrated that exposure to environments associated with alcohol intake reinstates alcohol seeking after extinction of alcohol-reinforced responding in a different context. However, extinction is limited as an abstinence model, because humans typically abstain because of negative consequences associated with excessive drinking. It is currently unknown whether alcohol-associated contexts can provoke relapse to alcohol seeking after alcohol-taking behavior is ...[more]

PMID: 22883434

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Project description:Evidence concerning the role of alcohol-induced neuroinflammation in alcohol intake and relapse has increased in the last few years. It is also proven that mu-opioid receptors (MORs) mediate the reinforcing properties of alcohol and, interestingly, previous research suggests that neuroinflammation and MORs could be related. Our objective is to study neuroinflammatory states and microglial activation, together with adaptations on MOR expression in the mesocorticolimbic system (MCLS) during the abstinence and relapse phases. To do so, we have used a sex-dependent rat model of complete Freund's adjuvant (CFA)-induced alcohol deprivation effect (ADE). Firstly, our results confirm that only CFA-treated female rats, the only experimental group that showed relapse-like behavior, exhibited specific alterations in the expression of phosphorylated NFκB, iNOS, and COX2 in the PFC and VTA. More interestingly, the analysis of the IBA1 expression revealed a decrease of the microglial activation in PFC during abstinence and an increase of its expression in the relapse phase, together with an augmentation of this activation in the NAc in both phases that only occur in female CFA-treated rats. Additionally, the expression of IL1β also evidenced these dynamic changes through these two phases following similar expression patterns in both areas. Furthermore, the expression of the cytokine IL10 showed a different profile than that of IL1β, indicating anti-inflammatory processes occurring only during abstinence in the PFC of CFA-female rats but neither during the reintroduction phase in PFC nor in the NAc. These data indicate a downregulation of microglial activation and pro-inflammatory processes during abstinence in the PFC, whereas an upregulation can be observed in the NAc during abstinence that is maintained during the reintroduction phase only in CFA-female rats. Secondly, our data reveal a correlation between the alterations observed in IL1β, IBA1 levels, and MOR levels in the PFC and NAc of CFA-treated female rats. Although premature, our data suggest that neuroinflammatory processes, together with neural adaptations involving MOR, might play an important role in alcohol relapse in female rats, so further investigations are warranted.

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Context-induced relapse to alcohol seeking after punishment in a rat model.

Publications

Context-induced relapse to alcohol seeking after punishment in a rat model.

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