Ventral tegmental area dopaminergic neurons mediate electroacupuncture relief of stress-induced depression in mice

Abstract

Aims: Depression is a prevalent mood disorder characterized by persistent low mood and cognitive deficits that severely impaired quality of life. Despite intensive research, its precise pathogenesis remained elusive, and a considerable proportion of patients were refractory to existing therapies. Recent work has highlighted ventral tegmental area (VTA) dopaminergic (DAergic) neurons in the pathophysiology of depression because of their central role in reward processing and motivation. In this study, we provided direct evidence that VTA^DA neurons were implicated in the alterations evoked by 21-day chronic restraint stress (CRS) in mice.

Materials and methods: Employing in vivo fiber photometry, chemogenetics, behavioral tests, and immunofluorescence, we investigated the effect of VTA^DA neurons of regulation on depressive behavior of the CRS mice.

Key findings: The activity of VTA^DA neurons was markedly decreased in CRS exposed animals. Chemogenetic activation of these neurons alleviated depression like symptoms, whereas their inhibition induced depression like phenotypes in the absence of stress. Electroacupuncture (EA) has garnered substantial clinical attention for mood disorders because of its established safety, minimal adverse effects, and robust therapeutic efficacy. Here, EA at specific acupoints reversed CRS induced behavioral deficits and restored VTA^DA neuron activity. However, chemogenetic inhibition of VTA^DA neurons during EA abolished its antidepressant effects.

Significance: Collectively, our findings provided mechanistic insight into the contribution of VTA^DA neurons to CRS induced depression.

Keywords: Chronic restraint stress; Depression; Electroacupuncture; VTA.