Incubation of discriminative stimulus-controlled cocaine craving: An animal model relevant to relapse prevention

In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency ('incubate') over time. Animal models of incubation may help develop treatments to prevent relapse, but these models have ubiquitously focused on the role of conditioned stimuli (CSs) signaling drug delivery. From a translational perspective this is problematic because people encounter these stimuli only during or after relapse. For this reason, incubation in response to discriminative stimuli (DSs) that signal drug availability before relapse, not yet examined in preclinical studies, could be more relevant to relapse prevention. We trained rats to self-administer cocaine (or palatable food) under DS control, then investigated DS-controlled incubation of craving, in the absence of drug-paired CSs. DS-controlled cocaine (but not palatable food) seeking incubated over 60 days of abstinence and persisted up to 300 days. Understanding the neural mechanisms of this DS-controlled incubation holds significant promise for drug relapse treatments.