Working Paper Article Version 2 This version is not peer-reviewed

Increased Excitability of Serotoninergic Neurons and Reduced Concentrations of Circulating Corticosteroids Two Weeks After Chronic Stress in Rats: Mechanisms Involved

Version 1 : Received: 27 February 2021 / Approved: 1 March 2021 / Online: 1 March 2021 (13:46:41 CET)
Version 2 : Received: 14 July 2021 / Approved: 15 July 2021 / Online: 15 July 2021 (10:40:31 CEST)

How to cite: Dremencov, E.; Grinchii, D.; Buzgoova, K.; Lapshin, M.; Komelkova, M.; Graban, J.; Tseilikman, O.; Tseilikman, V.; Jezova, D. Increased Excitability of Serotoninergic Neurons and Reduced Concentrations of Circulating Corticosteroids Two Weeks After Chronic Stress in Rats: Mechanisms Involved. Preprints 2021, 2021030018 Dremencov, E.; Grinchii, D.; Buzgoova, K.; Lapshin, M.; Komelkova, M.; Graban, J.; Tseilikman, O.; Tseilikman, V.; Jezova, D. Increased Excitability of Serotoninergic Neurons and Reduced Concentrations of Circulating Corticosteroids Two Weeks After Chronic Stress in Rats: Mechanisms Involved. Preprints 2021, 2021030018

Abstract

Exposure to predator scent (PS) has been used as a model of stress associated with danger to life and body integrity. We tested the hypothesis that repeated PS exposure alters the excitability of serotonin (5-HT) neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as cortical brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague-Dawley rats were exposed to PS for ten minutes daily for ten consecutive days. Two weeks after the last exposure, electrophysiological and biochemical assessments were performed. Measurements by in vivo electrophysiology showed increased spontaneous firing activity of 5-HT neurons in rats exposed to PS. PS exposure resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands, as well as the relative weight of the adrenals, were unaffected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. In conclusion, repeated exposure of rats to PS leads to enhanced firing activity of 5-HT neurons accompanied by reduced serum, but not adrenal aldosterone and corticosterone concentrations. Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tissue uptake rather than altered steroidogenesis. The decrease in circulating corticosterone in rats experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal firing activity might be an important compensatory mechanism designated to diminish the harmful effects of the repeated PS exposure on the brain.

Keywords

predator scent; aldosterone; corticosterone; adrenal gland; dorsal raphe nucleus (DRN); serotonin (5-HT); electrophysiology

Comments (1)

Comment 1
Received: 15 July 2021
Commenter: Eliyahu Dremencov
Commenter's Conflict of Interests: Author
Comment: It is a revised version of our manuscript "Effect of repeated predator scent exposure on excitability of serotonin neurons and stress markers in rats" which was previously submitted to the IJMS. It is revised in accordance with the recommendations of the editorial board. New molecular studies supporting the working hypothesis were added. The title and the abstract were amended to make them more corresponding to the main message of the study.
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