Transcutaneous Auricular Vagus Nerve Stimulation Mediates Antidepressant Effects by Altering Right Brainstem and Right Entorhinal Cortex Activity in a Rodent Model Functional Dyspepsia

OBJECTIVE: Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to ameliorate symptoms of both functional dyspepsia (FD) and depression/anxiety, while the central mechanism underlying taVNS effects on depression and anxiety in FD remains unclear. The aim of this study was to investigate taVNS-induced depression-like behavioral changes and cerebral activity alterations in a rodent model of FD. METHODS: Neonatal Sprague-Dawley (SD) rats were gavaged with iodoacetamide (IA) to induce a FD model. taVNS was performed for 30 min once daily for 14 days consecutively. The open field test (OFT) and forced swimming test (FST) were conducted to assess depression-like behaviors. The amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo) were derived from resting-state functional magnetic resonance imaging. Correlations between differential ALFF and ReHo values and depression-like behaviors were analyzed to identify taVNS-related central changes. RESULTS: taVNS increased both horizontal and vertical scores in the OFT and reduced the immobility time of the FST. After taVNS intervention, the ALFF and ReHo values of the right brainstem were decreased. Conversely, the ALFF values of the left molecular layer of the cerebellum and the ReHo values of the right entorhinal cortex were increased. The horizontal score of the OFT was negatively correlated with the ALFF of the right brainstem. Both the vertical score of the OFT and the immobility time of the FST were negatively correlated with the ReHo values of the entorhinal cortex. CONCLUSION: taVNS alleviates depressive state in FD rats, possibly mediated by enhancing local neural coordination in the right entorhinal cortex and suppressing spontaneous neural activity in the right brainstem. These findings support further exploration of taVNS as a candidate approach for FD-related depression.