Pavlovian-conditioned alcohol-seeking behavior in rats is invigorated by the interaction between discrete and contextual alcohol cues: Implications for relapse

Introduction: Drug craving can be independently stimulated by cues that are directly associated with drug intake (discrete drug cues), as well as by environmental contexts in which drug use occurs (contextual drug cues). We tested the hypothesis that the context in which a discrete alcohol-predictive cue is experienced can influence how robustly that cue stimulates alcohol-seeking behavior. Methods: Male, Long-Evans rats received Pavlovian discrimination training (PDT) sessions in which one conditioned stimulus (CS+; 16 trials/session) was paired with ethanol (0.2 mL/CS+) and a second stimulus (CS-; 16 trials/session) was not. PDT occurred in a specific context, and entries into a fluid port where ethanol was delivered were measured during each CS. Next, rats were acclimated to an alternate (nonalcohol) context where cues and ethanol were withheld. Responses to the nonextinguished CS+ and CS- were then tested without ethanol in the alcohol-associated PDT context, the nonalcohol context or a third, novel context. Results: Across PDT the CS+ elicited more port entries than the CS-, indicative of Pavlovian discrimination learning. At test, the CS+ elicited more port entries than the CS- in all three contexts: however, alcohol seeking driven by the CS+ was more robust in the alcohol-associated context. In a separate experiment, extinguishing the context-alcohol association did not influence subsequent CS+ responding but reduced alcohol seeking during non-CS+ intervals during a spontaneous recovery test. Conclusion: These results indicate that alcohol-seeking behavior driven by a discrete Pavlovian alcohol cue is strongly invigorated by an alcohol context, and suggest that contexts may function as excitatory Pavlovian conditioned stimuli that directly trigger alcohol-seeking behavior.