Transcutaneous auricular vagus nerve stimulation triggers melatonin secretion and is antidepressive in Zucker diabetic fatty rats.

Shaoyuan Li,Hui Ben,Peijing Rong,Michael F Mccabe,Jingjun Zhao,Xu Zhai,Shuxing Wang,Xing Wang,David A Slattery

doi:10.1371/journal.pone.0111100

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.

Highlights

A craving for the understanding of major depressive disorder makes the search for additional animal models highly necessary
Based on the existence of overt depression in Zucker diabetic fatty (ZDF) rats [2] as well as the increasingly prevalent comorbidity of obesity and depression [15], in this study we show that ZDF rats are ideal depression animal model and that the mechanism of the antidepressive effect of transcutaneous auricular vagus nerve stimulation (taVNS) is due to an enhanced tidal release of pineal and extrapineal melatonin
Tidal melatonin secretion upon taVNS treatment The acute effect of taVNS on melatonin level is shown in figure 2

Summary

Introduction

A craving for the understanding of major depressive disorder makes the search for additional animal models highly necessary. Proper animal models would accelerate the understanding of the etiology of depression and development of therapeutic approaches. Decreased level of circulating melatonin [4,5] and dysfunction of melatonin receptor type 1 [3] is contributable to depression. Complementary with melatonin is associated with reduced depression in rats [4,5] and patients [6,7]. The melatonin effect was shorter lasting [8], finding approaches that can maintain melatonin secretion will be helpful to clinical patients

Methods

Results

Conclusion