Abstract
Conditioned responding can be renewed by re-exposure to the conditioning context following extinction in a different context (ABA renewal) or by removal from the extinction context (AAB or ABC renewal). ABA renewal is robust in Pavlovian and operant conditioning paradigms. However, fewer studies have investigated AAB and ABC renewal of appetitive conditioning, and those that did predominantly used operant conditioning tasks. Renewal has theoretical relevance for extinction and for exposure-based treatments for substance use disorders that aim to extinguish reactivity to drug-predictive cues. We therefore investigated ABA, AAB, and ABC renewal of Pavlovian conditioned responding to cues that predicted either alcohol or sucrose. Male, Long-Evans rats (Charles River) were exposed to either 15% ethanol (Study 1: “alcohol”) or 10% sucrose (Study 2: “sucrose”) in their home cages. Next, they were trained to discriminate between two auditory stimuli (white noise and clicker; 10 s) in conditioning chambers equipped with distinct olfactory, visual, and tactile contextual stimuli (context A). One conditioned stimulus (CS+) was paired with fluid delivery (0.2 ml/CS+; 3.2 ml/session; alcohol or sucrose in separate experiments), and the second CS (CS−) was not. In all sessions (conditioning, extinction, and test), each CS was presented 16 times/session on a variable-time 67-s schedule, and entries into the fluid port were recorded. CS+ port entries were then extinguished by withholding fluid delivery either in context A or in a second, different context (context B). Next, we assessed ABA, AAB, and ABC renewal in the absence of fluid delivery. During extinction, CS+ port entries were initially elevated in context A relative to context B. ABA renewal of CS+ port entries occurred in both alcohol- and sucrose-trained rats. ABC renewal approached statistical significance when data from both experiments were combined. No AAB renewal was observed, and, in fact, alcohol-trained rats showed AAB suppression. These results corroborate the reliability of ABA renewal and suggest that ABC renewal is a modest effect that may require greater statistical power to detect. From a treatment perspective, the lack of AAB renewal suggests that exposure-based treatments for substance use disorders might benefit from implementation in real-world, drug-use contexts.
Highlights
Substance use disorders represent a global health crisis, and effective treatments are still needed (Degenhardt et al, 2013; Whiteford et al, 2013)
conditioned stimulus (CS)+ port entries at test in context C did not differ from the extinction in context B (p = 0.20) or from that in context A (p = 0.23). These results support visual inspection of the data, which suggest that ABC renewal occurred in a subset of rats but was overall less consistent than ABA renewal
AAB renewal has been reported in aversive Pavlovian conditioning studies (Bouton and Bolles, 1979; Tamai and Nakajima, 2000), we found no evidence of AAB renewal in either alcohol- or sucrose-trained rats
Summary
Substance use disorders represent a global health crisis, and effective treatments are still needed (Degenhardt et al, 2013; Whiteford et al, 2013). Exposure-based treatment aims to reduce the capacity of drug-predictive cues to impact relapse Gains from this approach may be transient and confined to the treatment context (Monti et al, 1993; Drummond and Glautier, 1994; Carter and Tiffany, 1999; Miller et al, 2001; Conklin and Tiffany, 2002; Bouton et al, 2012; Mellentin et al, 2017). ABA renewal has been widely reported in aversive Pavlovian conditioning paradigms (Bouton and Bolles, 1979; Bouton and King, 1983; Ji and Maren, 2005; Fujiwara et al, 2012) and has important implications for the nature of extinction (Rescorla, 1993; Bouton et al, 2011) It suggests that extinction does not permanently erase the original CS–US association that was acquired during conditioning. Renewal was tested in a new context following training and extinction in either the same (AAB renewal) or different (ABC renewal) contexts (Gunther et al, 1998; Harris et al, 2000; Corcoran and Maren, 2004; Thomas et al, 2004)
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