1. Anti-depressive mechanism of repetitive transcranial magnetic stimulation in rat: the role of the endocannabinoid system.
- Author
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Wang HN, Wang L, Zhang RG, Chen YC, Liu L, Gao F, Nie H, Hou WG, Peng ZW, and Tan Q
- Subjects
- Analysis of Variance, Animals, Brain-Derived Neurotrophic Factor metabolism, Bromodeoxyuridine, Cell Proliferation radiation effects, Disease Models, Animal, Exploratory Behavior drug effects, Exploratory Behavior radiation effects, Food Preferences drug effects, Food Preferences radiation effects, Male, Piperidines pharmacology, Proto-Oncogene Proteins c-bcl-2 metabolism, Pyrazoles pharmacology, Rats, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Swimming psychology, bcl-2-Associated X Protein metabolism, Depression pathology, Depression therapy, Gene Expression Regulation radiation effects, Hippocampus metabolism, Receptor, Cannabinoid, CB1 metabolism, Transcranial Magnetic Stimulation methods
- Abstract
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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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