title: Optimization of vagus nerve stimulation parameters using the firing activity of serotonin neurons in the rat dorsal raphe.
abstract: 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 micros, 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.
authors.affiliation: Institute of Mental Health Research, University of Ottawa, 1145 Carling Avenue, Ottawa, Ontario K1Z7K4, Canada. stella.manta@rohcg.on.ca
authors.forename: Stella
authors.initials: S
authors.lastname: Manta
authors.forename: Jianming
authors.initials: J
authors.lastname: Dong
authors.forename: Guy
authors.initials: G
authors.lastname: Debonnel
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000344:Afferent Pathways / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D004558:Electric Stimulation / Q000379:methods; D004567:Electrodes, Implanted; D008297:Male; D009474:Neurons / Q000502:physiology*; D011903:Raphe Nuclei / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D055536:Vagus Nerve Stimulation / Q000379:methods*
chemical_list: D012701:Serotonin