Deep Brain Stimulation of the Nucleus Accumbens Modulates Effort-Based Decision-Making and Phasic Dopamine Release in...

The initiation and sustained expression of motivated behaviour is strongly regulated by mesolimbic dopamine (DA) release within the nucleus accumbens (NAc). Deep brain stimulation (DBS) has demonstrated efficacy in treating refractory psychiatric disorders characterised by dysfunctional motivated drive and related behaviours. However, the neurobiological mechanisms underlying DBS effects at the local and circuit levels remain unclear. This study aimed to investigate the effects of NAc DBS on effort-based decision-making and local phasic DA neurotransmission in male Wistar rats. Male Wistar rats (N = 8) were trained on a concurrent fixed ratio 5/chow effort-related choice task (ERCT) until stable baseline performance was reached. On the test day, animals underwent a 2-h session of high-frequency NAc DBS (130 Hz; 90 μs pulse width; 500 μA) immediately prior to behavioural testing, with additional testing conducted on subsequent days to assess prolonged effects. In a separate experiment, the effects of identical NAc DBS parameters (or sham) on ventral tegmental area (VTA)-evoked (120 pulses; 60 Hz; 2 ms pulse width; 200-500 μA) DA release in the NAc core were quantified using fast-scan cyclic voltammetry in urethane-anesthetised rats (N = 12). Acute bilateral NAc DBS transiently reduced overall food-related motivation while maintaining effort-based choice bias. In parallel, NAc DBS significantly suppressed VTA-evoked NAc DA release compared to sham, although a moderate reduction was also observed in sham controls. DA reuptake kinetics remained unchanged across groups. NAc DBS transiently suppresses overall food-related motivation while maintaining effort-based decision-making. Attenuated phasic DA neurotransmission with active DBS may contribute to this behavioural effect.