Abstract
IntroductionDrug 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.MethodsMale, 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.ResultsAcross 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.ConclusionThese 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.
Highlights
Drug craving can be independently stimulated by cues that are directly associated with drug intake, as well as by environmental contexts in which drug use occurs
Determining how discrete and contextual drug cues independently influence relapse has been a long-standing empirical question. Given that these two types of environmental stimuli frequently co-occur in the everyday experience of drug users, it is of value to understand the impact that their co-occurrence may have on craving and drug seeking (Litt and Cooney 1999; Paris et al 2011; Nees et al 2012). We investigated this question using a behavioral animal model of Pavlovian-conditioned alcohol seeking in which rats were trained in a specific context to discriminate between two auditory conditioned stimuli (CS), a CS+ that was paired with alcohol and a CSÀ that was presented without alcohol (Chaudhri et al 2008b, 2010)
analysis of variance (ANOVA) conducted on normalized CS responding (Fig. 2A) revealed a significant main effect of CS (F(1, 15) = 46.90, P < 0.001), and follow-up t-tests for paired-samples verified a significant difference responding to the CS+ and the CSÀ in the alcohol context (t(15) = 5.70, P < 0.001) and nonalcohol context (t(15) = 4.86, P < 0.001)
Summary
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). Responses to the nonextinguished CS+ and CSÀ were 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 CSÀ, indicative of Pavlovian discrimination learning. The CS+ elicited more port entries than the CSÀ in all three contexts: alcohol seeking driven by the CS+ was more robust in the alcoholassociated context. 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.
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