Conditioned stimuli’s role in relapse: preclinical research on Pavlovian-Instrumental-Transfer

Abstract

Rationale and Objective Pavlovian learning is central to many theories of addiction. In these theories, stimuli paired with drug ingestion become Conditioned Stimuli (CS) and subsequently elicit drug-seeking and -taking. However in most relevant studies, Pavlovian and instrumental learning are confounded. This confound may be avoided in Pavlovian-Instrumental-Transfer (PIT) procedures. In PIT, Pavlovian and instrumental learning are established separately, and then combined. In order to better understand the role of CSs in addiction, we review the relevant studies using PIT. Findings We identified seven articles examining PIT effects of ethanol- or cocaine-paired CSs. Under at least one condition six of these articles reported CS-elicited increases in responding previously maintained by drug. However, the only study using the optimal control condition failed to find a CS-elicited increase. Two studies examining CS specificity found the CS also increased responding maintained by a different reinforcer. Two studies examined if CSs elicit increases in actual drug-taking. Both failed to find CS-elicited increases, i.e., no study shows CS-elicited increases in actual drug-taking. Further, CS-elicited increases in extinguished responding are short-lived. Conclusions These findings are not entirely consistent with Pavlovian learning playing a central role in addiction. However, design issues can explain most of these inconsistencies. Studies without these design issues are needed. Additionally, existing theories hypothesize drug-paired CSs increase drug-taking by increasing motivation, by eliciting conditioned responses that make drug-seeking more probable, or by a combination of these. Work distinguishing between these mechanisms would also be useful.

Effects of an ethanol-paired CS on responding for ethanol and food: Comparisons with a stimulus in a Truly-Random-Control group and to a food-paired CS on responding for food

“…When the light was located above the lever, approach towards the light increased the probability of a response; but when the light was located away from the lever, approach towards the light reduced the probability of a response. Such a hypothesis provides an alternative way of understanding the role of associative learning in addiction (Krank 2003; Krank et al 2008; Tomie 1995; Lamb et al 2016a; for yet another way see Hogarth et al 2013) to theories that hypothesize motivational effects of drug-paired stimuli.…”

“…Sometimes no facilitation will be seen (Experiment 1) and sometimes an ethanol-paired CS will even suppress ethanol responding (Krank 2003). The effects of an ethanol-paired CS may depend upon the CRs it elicits and the relationship between these CRs and the responses required to obtain ethanol (see Krank 2003; Lamb et al 2016a). The importance of this relationship and how it can be a natural consequence of drinking and drug use in many environments is a key feature of Tomie’s theory on the role of stimuli in addiction (Tomie 1995).…”

“…So, preclinical research is often used to examine this role. However, there are several important knowledge gaps in what can be taken away from the existing preclinical literature on the role of associative learning in addiction (Lamb et al 2016a). Stimuli paired with the effects of an abused drug can come to elicit conditioned responses (CR) that for the most part resemble the actions of the drug (see Eikelboom & Stewart 1984).…”

Conditioned Stimulus Form Does Not Explain Failures to See Pavlovian‐Instrumental‐Transfer With Ethanol‐Paired Conditioned Stimuli

“…The comparisons made in the various studies also must be considered (see Lamb et al 2016c). Comparisons to responding immediately proceeding CS presentation to responding during the CS presentation usefully controls for between subject differences in overall propensity to respond and changes in this propensity as extinction occurs during the test session ( e.g ., experiment 1 of this report and Glassner et al 2005).…”

“…However, isolating this role can be difficult with most commonly used procedures (see Lamb et al 2016c). One procedure thought to effectively isolate the role of associative learning upon operant responding, like drug seeking, is Pavlovian-Instrumental-Transfer (PIT; Estes, 1943).…”