Optimization of vagus nerve stimulation parameters using the firing activity of serotonin neurons in the rat dorsal raphe

Vagus nerve stimulation (VNS) is a recently approved adjunctive intervention for treatment-resistant depression. This therapy enhances the firing rate of rat norepinephrine neurons after 1 h and that of serotonin (5-HT) neurons only after 14 days. Various stimulation parameters were thus tested on their capacity to enhance 5-HT neuronal firing because of the delayed action of VNS on the 5-HT system and its important role in the antidepressant response. Rats were implanted with a stimulator and treated for 14 days, each group of rats having only one stimulation parameter modified from the standard ones (0.25 mA, 20 Hz, 500 µs, 30 s ON/5 min OFF). Electrophysiological recordings showed that the usual parameters utilized in depressed patients, with the exception of current intensity, produced an optimal activation of 5-HT neurons. Excessive enhancement of the charge delivered to the nerve can lead to a loss of VNS effect on 5-HT neuronal firing.