Comparing ABA, AAB, and ABC Renewal of Appetitive Pavlovian Conditioned Responding in Alcohol- and Sucrose-Trained Male Rats

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 exposurebased 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.

Associative processes in addiction relapse models: A review of their Pavlovian and instrumental mechanisms, history, and terminology

“…Similar results have been seen in an appetitive Pavlovian design, where ABA renewal was observed with both alcohol and sucrose reinforcers [78]. However, neither AAB nor ABC renewal was observed with either reinforcer [78]. Similarly, Crombag and colleagues did not observe AAB renewal following self-administration of a cocaineheroin mixture [87] and Fuchs and colleagues observed ABA but not AAB renewal of cocaine self-administration [90].…”

“…For example, Zironi and colleagues tested rats trained to self-administer alcohol in a novel context (ABC renewal) and did not observe significant recovery while rats trained to self-administer sucrose did show ABC renewal [77]. Similar results have been seen in an appetitive Pavlovian design, where ABA renewal was observed with both alcohol and sucrose reinforcers [78]. However, neither AAB nor ABC renewal was observed with either reinforcer [78].…”

“…Bossert and colleagues also did not observe AAB renewal of heroin selfadministration [88], nor was AAB renewal for nicotine observed by Diergaarde and colleagues [89]. Prior studies that have shown AAB or ABC renewal in operant designs have all used food pellets or sucrose as reinforcers [78,[91][92][93]. In instrumental studies with food reinforcers, manipulations such as conducting acquisition training in multiple contexts have been shown to enhance ABC renewal [94], indicating the potential for improved generalisation of the acquisition memory to promote ABC renewal in addiction studies.…”

“…One potential point of contention is that Bouton and colleagues have conceptualised resurgence as renewal due to a novel context ('C') that is distinct from both the acquisition context ('A') and the extinction context ('B'), also known as ABC renewal [14]. However, attempts to show ABC renewal in alcohol have not been successful in either an operant design [77] or Pavlovian design [78]. It is therefore possible that resurgence in drug self-administration studies may be driven by factors other than contexts, underscoring the importance of understanding the behavioural mechanisms which drive resurgence as an avenue for further research.…”

Inhibitory control hinders habit change

“…Our findings in the Testing phase show that relapse can occur not only when human participants encounter the original context e.g. 33 , 34 (akin to extinction learning studies) but also in the new context. This suggests that inhibiting unwanted behavior in everyday situations is ineffective in changing habits e.g.…”