title: Transcutaneous auricular vagus nerve stimulation triggers melatonin secretion and is antidepressive in Zucker diabetic fatty rats.
abstract: Decreased circulating melatonin is implicated in depression. We recently found that Zucker diabetic fatty rats (ZDF, fa/fa) develop depression-like behaviors and that transcutaneous auricular vagus nerve stimulation (taVNS) is antidepressive in ZDF rats. Here we studied whether the ZDF rats could be used as a depression rodent model and whether the antidepressive effect of taVNS is mediated through modulation of melatonin secretion. Adult male ZDF and Zucker lean (ZL, fa/+) littermates were used. 30 min-taVNS procedures (2/15 Hz, 2 mA) were administered once daily under anesthesia for 34 consecutive days in pineal intact ZDF (n = 8) and ZL (n = 6) rats, as well as in pinealectomized ZDF rats (n = 8). Forced swimming test (FST) was used to determine depression-like behavior and ELISA to detect plasma melatonin concentration on day 35. We found that naïve ZDF rats had a longer immobility time in FST and that long-term (34 days) taVNS treatment ameliorated the depression-like behavior. In both pineal intact and pinealectomized ZDF rats, taVNS induced acute melatonin secretion, both during and after the taVNS session. A low melatonin level is related to the poor FST performance in ZDF rats (R = -0.544) in contrast to ZL rats (R = 0.247). In conclusion, our results show that ZDF rats are ideal candidates of innate depression and that taVNS is antidepressive through triggering melatonin secretion and increasing its production.
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China; Department of Anatomy, Xinxiang Medical University, Xinxiang, Henan Province, China.
authors.forename: Shaoyuan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Peijing
authors.initials: P
authors.lastname: Rong
authors.affiliation: Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Michael F
authors.initials: MF
authors.lastname: McCabe
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ben
authors.affiliation: Department of Anatomy, Xinxiang Medical University, Xinxiang, Henan Province, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China; Department of Anatomy, Xinxiang Medical University, Xinxiang, Henan Province, China; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Shuxing
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D003863:Depression / Q000097:blood / Q000209:etiology / Q000628:therapy*; D048909:Diabetes Complications / Q000097:blood / Q000628:therapy*; D008297:Male; D008550:Melatonin / Q000097:blood* / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D004561:Transcutaneous Electric Nerve Stimulation; D055536:Vagus Nerve Stimulation
chemical_list: D008550:Melatonin