Electrical stimulation rescues dopaminergic degeneration in dorsal raphe nucleus and enhanced hippocampal neurogenesis of vulnerable depressive-like rats

Abstract

Electrical stimulation is a potential treatment for patients with depression. In this study, we investigate the effects of high-frequency stimulation (HFS) on various depressive-like behaviours using the stress resilience and vulnerable rat depression models. Our results demonstrated that animals with 3 weeks chronic unpredictable stress (CUS) induced exhibition of reduced sucrose consumption in 51% of animals, thus separating the resilience and vulnerable group of CUS-induced model. CUS vulnerable sham animals demonstrated anxiety-like behaviour, decreased motivation and increased immobility compared to that of the resilience group, implicating high susceptibility of vulnerable individuals to the CUS procedure. Interestingly, vmPFC HFS significantly reduced anxiety response, increased hedonia and motivation levels for food intake in the vulnerable group compared to the resilience group. HFS in ventromedial prefrontal cortex (vmPFC) and lateral habenula also showed reduced behavioural despair in both CUS vulnerable and resilience groups. In histochemistry, our results demonstrate that vmPFC HFS rescued the stress-induced dopamine neuron degeneration in the dorsal raphe nucleus, as well as increased hippocampal neurogenesis in stress vulnerable animals. In conclusion, these results suggest that vmPFC HFS effectively restores depressive-like behaviours by mechanisms of dorsal raphe dopaminergic neurons restoration and enhanced hippocampal neuroplasticity in the vulnerable CUS-induced model.