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.

Figure 1. Intermittent free-choice home-cage access to 20% alcohol leads to high alcohol intake and robust acquisition of operant self-administration

(A) Graphical representation of the experimental design, see Methods for details. (B) Mean±SEM alcohol intake in g/kg (left panel) and preference for 20% alcohol over water (right panel) during the 12 sessions of free-choice home-cage access to 20% alcohol. The standard errors for these data points are smaller than the symbol size. (C) Mean±SEM alcohol intake in g/kg (left panel) and active lever-presses (right panel) during the three different 20% alcohol self-administration schedules: FR-1, 3 sessions, FR-5, 4 sessions, VI-30, 4 sessions (n=42).

Figure 2. Relapse to alcohol seeking when rats returned to the original training context after response-contingent punishment in an alternative context

(A) Mean±SEM reinforced active lever-presses during the final self-administration session in the initial training context (context A) and all self-administration sessions in the punishment context (context B). The numbers within the symbol represent n per group for each session. After the 3^rd session, rats in group Punished with more than 20 active lever-presses in the 2-h session were given additional sessions with increased shock intensity; rats from the other groups were given additional sessions to match this. (B) Mean±SEM non-reinforced active lever-lever-presspresses during the relapse tests in context B (left panel) and context A (right panel). Lever-presses of the Punished rats (n=15) were higher in context A than in context B. Context switch had no effect on non-reinforced responding in the Unpunished (n=11) and Non-contingent Shock (n=8) groups. (C) The top panel shows active lever-presses during testing in each context for individual rats in group Punished. The bottom panel shows correlation plots of active lever-presses during testing as a function of the number of context B punishment sessions. * Different from the other experimental conditions, p<0.05.

Figure 3. Context-induced reinstatement of alcohol seeking after extinction training

(A) Mean±SEM reinforced active lever-presses during the final self-administration session (context A) and non-reinforced lever-presses (extinction) in context B. (B) Mean±SEM non-reinforced active lever-presses during the reinstatement tests in context A and context B. All rats were tested in both contexts and the order of testing was counterbalanced. (C) Total active lever-presses during test in each context for individual rats (n=8). * Different from Context B, p<0.05.