Vagus nerve stimulation during extinction learning reduces conditioned place preference and context-induced reinstatement of cocaine seeking.

backgroundDrug use causes the formation of strong cue/reward associations which persist long after cessation of drug-taking and contribute to the long-term risk of relapse. Extinguishing these associations may reduce cue-induced craving and relapse. Previously, we found that pairing vagus nerve stimulation (VNS) with extinction of cocaine self-administration reduces cue-induced reinstatement; however, it remains unclear whether this was primarily caused by extinguishing the context, the instrumental response, or both.

objectiveHypothesis: We hypothesized that VNS can facilitate the extinction of both contextual cues and instrumental responding.

methodsExtinction of context was first tested using Pavlovian conditioned place preference (CPP). Next, the impact of VNS on the extinction of instrumental responding was assessed under ABA and AAA context conditions. In each extinction context separate groups of rats were either provided the opportunity to perform the instrumental response, or the levers were retracted for the duration of extinction training. Reinstatement was induced by reintroduction of the conditioned stimuli and/or the drug-paired context. Data were analyzed using one-way or two-way repeated measures ANOVAs.

resultsVNS during extinction reduced reinstatement of CPP. VNS also reduced cue- and context-induced reinstatement of the instrumental response under both AAA and ABA conditions. The subjects' ability to engage with the lever during extinction was crucial for this effect. P values < 0.05 were considered significant.

conclusionsCraving occurs in response to a range of conditioned stimuli and contexts; VNS may improve outcomes of behavioral therapy by facilitating extinction of both an instrumental response and/or contextual cues.