Acute auricular vagus nerve stimulation decreases glucose metabolism measured by 18F-FDG PET uptake in subcortical rat brain

Abstract Background: Vagus nerve stimulation (VNS) has been explored as an adjunct treatment for neurological disorders, such as epilepsy, chronic migraine, pain, and depression, as well as for its potential modulation of the immune response. A non-invasive form of VNS is transcutaneous auricular VNS (aVNS). The combination of animal models with non-invasive brain imaging may lead to a better understanding of its mechanisms. The aim of this study was to evaluate the acute effect of electrical stimulation of the left vagus nerve on brain glucose metabolism in naïve rat. Methods: Five female Sprague-Dawley rats were anesthetised with isoflurane and imaged with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) on two separate days, 1) at baseline, and 2) after a unilateral aVNS protocol initiated 10 minutes after 18F-FDG injection. The protocol consisted of 30 minutes of unilateral aVNS (left ear – 500-ms train of 15 biphasic pulses every 30s (0.8 mA, 30 Hz, 100 μs)). PET acquisition on both days was performed for 30 minutes at 45 minutes after 18F-FDG injection, and data were analyzed using PMODÔ. Standard uptake values (SUV) of the brain regions of interest were calculated. Baseline versus aVNS data were compared with paired t tests for each brain region, and significance was set at p < 0.05. Results: Significantly decreased 18F-FDG uptake was observed bilaterally in ventral tegmental area (13.5%), nucleus accumbens (11%), amygdala (14%), hypothalamus (13%) and hippocampus (10%) after aVNS. Conclusions: This proof-of-concept study shows decreased subcortical glucose metabolism in vivo in response to acute aVNS. The reduced uptake in limbic brain regions may, for example, shed light on the antidepressant potential of aVNS. We suggest that the use of disease models undergoing acute or chronic brain stimulation, and PET ligands of different targets, may be a powerful combination to assess the therapeutic potential of aVNS. Research Category and Technology and Methods Basic Research: 12. Vagus Nerve Stimulation (VNS) Keywords: auricular vagus nerve stimulation, glucose metabolism, brain metabolism, non-invasive therapy