The effects of unilateral transcutaneous auricular vagus nerve stimulation on pineal melatonin levels in Zucker lean and Zucker diabetic obese (ZDO) rats was investigated (Li et al., 2014). Stimulation was applied once during the day-time to the right auricular concha region via opposing magnetic electrodes. Stimulation frequency switched every second between 2 and 15 Hz at a current of 2 mA. Following 34 consecutive days of stimulation, plasma melatonin levels in stimulated ZDO rats was significantly higher compared to non-stimulated controls. Furthermore, this elevated concentration was detectable for over 20 h after the final stimulation session. Notably, the experimenters investigated the effect of transauricular vagus nerve stimulation (taVNS) on pinealectomised ZDO rats and were still able to observe acute increases in plasma melatonin levels similar to that seen in intact ZDO rats. Similar results were also achieved 1 year later using bilateral taVNS (Wang et al., 2015). As increases in melatonin were still observed despite removal of the pineal gland, this indicates that vagus nerve stimulation prompts secretion of melatonin from extrapineal sites rather than from the gland itself. However, since usual pinealectomy removes only the superficial portion of the gland, leaving the deep pineal intact, one cannot discount the possibility that circulating melatonin levels may be due to contribution from the deep portion of the gland. Yet, atrophy of the deep pineal is apparent following superficial pinealectomy in rats (Heidbuchel and Vollrath, 1983), which most likely results in impaired function, although this has not been confirmed. This is not surprising since the sympathetic fibres that innervate the gland first supply the superficial pineal before coursing down the stalk and supplying innervation to the deep pineal. This suggests that removal of the superficial pineal disrupts the sympathetic input to the deep pineal, which would account for the observed atrophy. If sympathetic input is disrupted, then one may speculate that the likelihood of the deep pineal contributing to systemic melatonin levels is low.
https://www.frontiersin.org/articles/10.3389/fnins.2020.00264/full
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