Deep Brain Stimulation of the Nucleus Accumbens Core Affects Trait Impulsivity in a Baseline-Dependent Manner

Abstract

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.

Deep brain stimulation of the nucleus accumbens shell does not decrease cocaine self-administration in cocaine-dependent rats but increases GluR1/GluA1 in the central nucleus of the amygdala

“…For DBS, we used bilateral, monophasic (60 µs pulse width and 130 Hz frequency) stimulation with a constant current of 150 µA. These parameters are consistent with previous studies in the field that used high-frequency stimulation (HFS; [21,[32][33][34]. After a stable level of self-administration was achieved, the effects of DBS on cocaine self-administration in cocaine-dependent rats was evaluated for 4 consecutive days, with 2 "ON" and 2 "OFF" sessions on alternate days.…”

An automated home-cage-based 5-choice serial reaction time task for rapid assessment of attention and impulsivity in rats

“…In SP-5-CSRTT, time-out periods were signaled by turning on the house-light. Despite this, behavioral challenges, such as varying ITI or SD, resulted in similar effects to conventional 5-CSRTT (Bari et al 2008; Saund et al 2017; Schippers et al 2017). Varying the ITI led to increased premature responding and decreased omissions.…”

“…Varying the ITI led to increased premature responding and decreased omissions. Increasing ITI durations has previously been reported to lower omissions in rats (Schippers et al 2017), yet increases in omissions have also been shown (Chudasama et al 2003; Saund et al 2017). This may result from shorter limited hold periods urging faster responses following stimulus presentation.…”

High trait impulsivity potentiates the effects of chronic pain on impulsive behavior

“…In the NAc, HI animals present a decreased availability of D1 and D2/3 receptors and of dopamine transporter (DAT) (Caprioli et al, 2015, Jupp et al, 2013) as well as a reduction in grey matter density (Caprioli et al, 2014). Interestingly, deep brain stimulation in the NAc decreases impulsivity particularly in HI animals (Schippers et al, 2017). The NAc has been involved in chronic pain – see for review (Benarroch, 2016, Mitsi and Zachariou, 2016) – and appears as a prime candidate to mediate decision-making and motivational alterations observed in chronic pain models.…”