Transcutaneous auricular vagus nerve stimulation in anesthetized mice induces antidepressant effects by activating dopaminergic neurons in the ventral tegmental area

Depression, a prevalent neuropsychiatric disorder, involves the dysregulation of neurotransmitters such as dopamine (DA). The restoration of DA balance is a pivotal therapeutic target for this condition. Recent studies have indicated that both antidepressant medications and non-pharmacological treatments, such as transcutaneous auricular vagus nerve stimulation (taVNS), can promote recovery from depressive symptoms. Despite the promise of taVNS as a non-invasive depression therapy, its precise mechanism remains unclear. We hypothesized that taVNS exerts antidepressant effects by modulating the DAergic system. To investigate this, we conducted experiments demonstrating that taVNS in anesthetized mice reduced depressive-like behaviors. However, this effect was abolished when DA neurons in the ventral tegmental area (VTA^DA) were inhibited. Additionally, taVNS in anesthetized mice enhanced VTA^DA activity, providing further evidence to support its antidepressant effects. Overall, our findings suggest that taVNS alleviates depression by augmenting VTA^DA activity, thereby contributing to a more comprehensive understanding of its therapeutic mechanisms.