PMID- 24479995 OWN - NLM STAT- MEDLINE DCOM- 20141014 LR - 20161125 IS - 1879-1379 (Electronic) IS - 0022-3956 (Linking) VI - 51 DP - 2014 Apr TI - Anti-depressive mechanism of repetitive transcranial magnetic stimulation in rat: the role of the endocannabinoid system. PG - 79-87 LID - S0022-3956(14)00005-3 [pii] LID - 10.1016/j.jpsychires.2014.01.004 [doi] AB - Repetitive transcranial magnetic stimulation (rTMS) to treat depression has been thoroughly investigated in recent years. However, the underlying mechanisms are not fully understood. In this study, a chronic unpredictable mild stress (CUMS) paradigm was applied to male Sprague Dawley rats. Then rTMS was performed for 7 consecutive days, and the anti-depressive effects were evaluated by the sucrose preference test (SPT), the forced swimming test (FST), and the open-field test (OFT). Hippocampal cannabinoid type I receptor (CB1) expression was measured, and the expression levels of brain-derived neurotrophic factor (BDNF), Bcl-2, and Bax and the number of bromodeoxyuridine (BrdU)-positive cells were also investigated. These parameters were also observed after the selective CB1 receptor antagonist AM251 was used as a blocking agent. The results showed that CUMS induced a significant decrease in sucrose preference, a significant increase in immobility time in the FST, and a significantly decreased horizontal distance in the OFT. In addition, reduced hippocampal CB1 receptor, BDNF, and Bcl-2/Bax protein expression levels in CUMS rats, as well as decreased cell proliferation were also observed in the dentate gyrus. Meanwhile, rTMS treatment up-regulated cell proliferation; elevated CB1 receptor, BDNF, and Bcl-2/Bax expression levels in the hippocampus; and ameliorated depressive-like behaviors. All of these beneficial effects were abolished by AM251. These results indicate that rTMS increases BDNF production and hippocampal cell proliferation to protect against CUMS-induced changes through its effect on CB1 receptors. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Wang, Hua-ning AU - Wang HN AD - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China. FAU - Wang, Lei AU - Wang L AD - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China; Xi'an city mental health center, Xi'an, China. FAU - Zhang, Rui-guo AU - Zhang RG AD - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China. FAU - Chen, Yun-chun AU - Chen YC AD - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China. FAU - Liu, Ling AU - Liu L AD - Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China. FAU - Gao, Fang AU - Gao F AD - Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China. FAU - Nie, Huang AU - Nie H AD - Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. FAU - Hou, Wu-gang AU - Hou WG AD - Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. FAU - Peng, Zheng-wu AU - Peng ZW AD - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China; Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: pengzhengwu1446@163.com. FAU - Tan, Qingrong AU - Tan Q AD - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China. Electronic address: tanqingr@fmmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140117 PL - England TA - J Psychiatr Res JT - Journal of psychiatric research JID - 0376331 RN - 0 (Bax protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Piperidines) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Pyrazoles) RN - 0 (Receptor, Cannabinoid, CB1) RN - 0 (bcl-2-Associated X Protein) RN - 3I4FA44MAI (AM 251) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Analysis of Variance MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Bromodeoxyuridine MH - Cell Proliferation/radiation effects MH - Depression/*pathology/*therapy MH - Disease Models, Animal MH - Exploratory Behavior/drug effects/radiation effects MH - Food Preferences/drug effects/radiation effects MH - Gene Expression Regulation/*radiation effects MH - Hippocampus/*metabolism MH - Male MH - Piperidines/pharmacology MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Pyrazoles/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, Cannabinoid, CB1/antagonists & inhibitors/*metabolism MH - Swimming/psychology MH - Transcranial Magnetic Stimulation/*methods MH - bcl-2-Associated X Protein/metabolism OTO - NOTNLM OT - Cannabinoid type I receptor OT - Depression OT - Hippocampus OT - Repetitive transcranial magnetic stimulation EDAT- 2014/02/01 06:00 MHDA- 2014/10/15 06:00 CRDT- 2014/02/01 06:00 PHST- 2013/10/31 00:00 [received] PHST- 2013/12/11 00:00 [revised] PHST- 2014/01/08 00:00 [accepted] PHST- 2014/02/01 06:00 [entrez] PHST- 2014/02/01 06:00 [pubmed] PHST- 2014/10/15 06:00 [medline] AID - S0022-3956(14)00005-3 [pii] AID - 10.1016/j.jpsychires.2014.01.004 [doi] PST - ppublish SO - J Psychiatr Res. 2014 Apr;51:79-87. doi: 10.1016/j.jpsychires.2014.01.004. Epub 2014 Jan 17.