Deep brain stimulation (DBS) of the nucleus accumbens (NA) is explored as a treatment for refractory psychiatric disorders, such as obsessive-compulsive disorder (OCD), depressive disorder (MDD), and substance use disorder (SUD). A common feature of some of these disorders is pathological impulsivity. Here, the effects of NAcore DBS on impulsive choice and impulsive action, two distinct forms of impulsive behavior, were investigated in translational animal tasks, the delayed reward task (DRT) and five-choice serial reaction time task (5-CSRTT), respectively. In both tasks, the effects of NAcore DBS were negatively correlated with baseline impulsive behavior, with more pronounced effects in the 5-CSRTT. To further examine the effects of DBS on trait impulsive action, rats were screened for high (HI) and low (LI) impulsive responding in the 5-CSRTT. NAcore DBS decreased impulsive, premature responding in HI rats under conventional conditions. However, upon challenged conditions to increase impulsive responding, NAcore DBS did not alter impulsivity. These results strongly suggest a baseline-dependent effect of DBS on impulsivity, which is in line with clinical observations.

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 selfadministration 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.

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