Differential stimulus control of drug-seeking: multimodal reinstatement

Abstract

In animal models of substance-use disorder, individuals that repeatedly self-administer drugs of abuse have long-lasting neuronal adaptations that do not occur ostensibly in control animals only exposed to natural reinforcers (e.g. food). Because any treatment for substance-use disorder will be given to individuals with drug-taking histories, adequate dissociation of the specific neurobehavioral mechanisms underlying drug reinforcement, natural reinforcement and their associated cue effects requires an experimental model that exposes individuals to both reinforcer conditions, along with their associated stimuli. Furthermore, contingent stimuli that reinforce drug seeking through second-order relationships may produce reinstatement of drug seeking through different neurobehavioral means than non-contingent exposure to stimuli that signal the availability of a drug reinforcer, effectively producing different modes of stimulus-induced reinstatement. Toward experimental isolation of the relationships mentioned, herein, we used a within-session multiple schedule of reinforcement containing both discriminative (S^D ) and conditioned (CS) stimuli to study stimulus control of drug-taking and food-taking behavior, along with how these functionally distinct cues may differentially reinstate drug-seeking and food-seeking behavior within a single animal. We demonstrate specific stimulus control over drug and food taking; furthermore, we demonstrate that the same stimulus (i.e. cue light) operating as an S^D or CS produced differential reinstatement of drug-taking and food-taking behavior. The results suggest that contingent CSs and non-contingent S^D s produce reinstatement through different neurobehavioral processes and, within-session multiple schedules, can be used to study different modes of specific stimulus control over drug and food seeking in a single animal with both drug-taking and food-taking history.

Keywords: cocaine; conditioned stimulus; discriminative stimulus; methamphetamine; multiple schedule; reinstatement.