Abstract
BACKGROUND: Deep brain stimulation is explored as a new intervention for treatment-resistant substance use dependence. A candidate brain region is the nucleus accumbens, due to its involvement in reward and motivation. This study aimed to explore effects of NAcore and NAshell deep brain stimulation on aspects of heroin taking and seeking in a self-administration model for rats. METHODS: NAcore and NAshell deep brain stimulation was applied during 25 or 100 µg/kg/infusion heroin self-administration on an FR4 schedule of reinforcement and during cue- and heroin-induced reinstatement. In a separate group, effects of NAcore deep brain stimulation on heroin self-administration on a progressive ratio schedule and the first extinction session were examined. RESULTS: NAcore and NAshell deep brain stimulation did not alter heroin self-administration on an FR4 schedule. NAcore deep brain stimulation decreased cue - but not drug-induced reinstatement of heroin seeking, whereas NAshell deep brain stimulation did not affect reinstatement responding. In the second experiment, NAcore deep brain stimulation reduced responding during a progressive ratio schedule of heroin reinforcement. Finally, deep brain stimulation facilitated extinction from day 1 throughout the course of extinction learning. CONCLUSION: Taken together, the differential effects of NAcore and NAshell deep brain stimulation on heroin taking and seeking are in line with the distinct functional roles of these sub-regions therein. Conditioned cues have been shown to be very powerful stimuli for the persistence of addiction and relapse to drug use. Therefore, the present findings that NAcore deep brain stimulation decreases motivation for heroin taking and cue-conditioned behaviour and facilitates extinction learning are very promising, supporting the positive findings from clinical case studies.