Pavlovian-to-instrumental transfer in cocaine seeking rats.

Abstract

Drug-associated cues are believed to be important mediators of addiction and drug relapse. Although such cues may influence drug-seeking behavior through multiple routes, it is their putative incentive motivational properties-their ability to elicit "craving"-that interests many addiction researchers. The Pavlovian-to-instrumental transfer paradigm is commonly used to assay cue-evoked incentive motivation in situations involving natural rewards, but has not been widely applied to the study of drug self-administration. We used this paradigm to determine whether cues paired with intravenous cocaine could promote performance of an independently trained task in which rats self-administered cocaine by completing a chain of two different lever press actions, a procedure used to parse behavior into cocaine seeking (first action) and cocaine taking (second action). Rats showed significant transfer, increasing task performance during cocaine-paired cues. This effect was observed for both seeking and taking actions, although a trend toward greater cocaine taking was observed, a result that is consistent with studies using natural rewards. Our results demonstrate that cocaine-paired cues can provoke the pursuit of cocaine through a Pavlovian motivational process. This phenomenon may provide a useful new tool for modeling drug relapse, particularly as a method for targeting the response-invigorating effects of stimulus-drug learning.