Trial-based Discrimination Procedure for Studying Drug Relapse in Rats

In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency ('incubate') over time. Animal models of incubation may help in developing treatments for relapse prevention. However, these models have primarily focused on the role of conditioned stimuli (CSs) signaling drug delivery and not on discriminative stimuli (DSs), which signal drug availability and are also known to play a major role in drug relapse. We recently showed that DS-controlled cocaine seeking in rats also incubates during abstinence and persists up to 300 days. We used a trial-based procedure to train male and female rats to discriminate between two light cues: one light cue (DS+) signaled the availability of cocaine reward and the second light cue (DS-) signaled the absence of reward. Rats learned to press a central retractable lever during trials in which the DS+ cue was presented and to suppress responding when the DS- cue was presented. Here, we provide a detailed protocol for the behavioral procedure used in our study. The trial-based design of this behavior lends itself well to time-locked in vivo recording and manipulation approaches that can be used to identify neurobiological mechanisms underlying the contributions of DSs to drug relapse.