PMID- 30735600 OWN - NLM STAT- MEDLINE DCOM- 20200814 LR - 20200814 IS - 1460-9568 (Electronic) IS - 0953-816X (Linking) VI - 50 IP - 1 DP - 2019 Jul TI - Hippocampal activation of 5-HT(1B) receptors and BDNF production by vagus nerve stimulation in rats under chronic restraint stress. PG - 1820-1830 LID - 10.1111/ejn.14368 [doi] AB - A growing body of evidence shows that the electrical stimulation of the vagus nerve can improve mental illness including depression. Here, we investigated whether the vagus nerve stimulation (VNS) is involved in regulating the responsiveness of hippocampal neurons in rats under chronic restraint stress (CRS). c-Fos protein signals were detected 2 hr after VNS in 5-HT(1A) receptor-positive neurons in the dorsal raphe nucleus (DRN) as well as in the nucleus tractus solitarius (NTS). Chronic VNS was performed on a daily basis for 2 weeks using an implanted microelectrode in rats that had undergone CRS for 2 weeks. We found that the levels of both 5-HT(1B) receptors and phospho-Erk1/2 were decreased in parallel in the hippocampal neurons of CRS animals and then increased to the baseline levels by chronic VNS. Hippocampal induction of 5-HT(1B) receptors and phospho-Erk1/2 by VNS was diminished after the injection of 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin of serotonergic neurons, into the DRN. Hippocampal production of brain-derived neurotrophic factor (BDNF) was also upregulated by VNS, but the treatment of 5,7-DHT abrogated the effects of VNS on BDNF induction. VNS in CRS animals improved the behavioral scores in forced swimming test (FST) compared to sham-stimulated control. Our results suggest that VNS-mediated serotonergic input via 5-HT(1B) receptors into the hippocampal neurons may activate BDNF pathway and improve depressive-like behaviors in CRS animals. CI - (c) 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. FAU - Shin, Hwa Chul AU - Shin HC AD - Department of Oriental Medicine, Daejeon University, Daejeon, Korea. FAU - Jo, Byung Gon AU - Jo BG AD - Department of Oriental Medicine, Daejeon University, Daejeon, Korea. FAU - Lee, Chan-Yong AU - Lee CY AD - Department of Microbiology and Biotechnology, Daejeon University, Daejeon, Korea. FAU - Lee, Kang-Woo AU - Lee KW AD - Department of Oriental Medicine, Daejeon University, Daejeon, Korea. FAU - Namgung, Uk AU - Namgung U AUID- ORCID: 0000-0001-5253-1143 AD - Department of Oriental Medicine, Daejeon University, Daejeon, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190306 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptor, Serotonin, 5-HT1B) SB - IM MH - Animals MH - Behavior, Animal/*physiology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Depression/*metabolism/*therapy MH - Disease Models, Animal MH - Hippocampus/*metabolism MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, Serotonin, 5-HT1B/*metabolism MH - Restraint, Physical MH - Stress, Psychological/*metabolism/*therapy MH - *Vagus Nerve Stimulation OTO - NOTNLM OT - BDNF OT - Phospho-Erk1/2 OT - animal model OT - depression OT - dorsal raphe nucleus EDAT- 2019/02/09 06:00 MHDA- 2020/08/15 06:00 CRDT- 2019/02/09 06:00 PHST- 2018/06/26 00:00 [received] PHST- 2019/01/11 00:00 [revised] PHST- 2019/01/30 00:00 [accepted] PHST- 2019/02/09 06:00 [pubmed] PHST- 2020/08/15 06:00 [medline] PHST- 2019/02/09 06:00 [entrez] AID - 10.1111/ejn.14368 [doi] PST - ppublish SO - Eur J Neurosci. 2019 Jul;50(1):1820-1830. doi: 10.1111/ejn.14368. Epub 2019 Mar 6.