Nucleus accumbens high-frequency stimulation selectively impacts nigrostriatal dopaminergic neurons

Abstract

High-frequency stimulation of the nucleus accumbens, also known as deep brain stimulation (DBS), is currently used to alleviate obsessive compulsive symptoms when pharmacotherapy is ineffective. However, the mechanism by which DBS achieves its therapeutic actions is not understood. Imaging studies and the actions of dopaminergic drugs in untreated patients suggest that the dopamine (DA) system likely plays a role in the pathophysiology of obsessive compulsive disorder. Therefore, we examined whether DBS would impact the DA system as a potential component of its therapeutic actions. The activity of DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were recorded in anesthetized rats under high-frequency stimulation. DA neuron activity was measured in terms of number of neurons firing, average firing rate and firing pattern. DBS of the nucleus accumbens core did not significantly affect VTA activity or discharge pattern. On the other hand, DBS caused a potent decrease in the number of SNc DA neurons firing spontaneously. Such an effect could contribute to the disruption of pathological habit formation in the SNc-dorsal striatal projection system that may have therapeutic implications for the treatment of obsessive compulsive disorder.