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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 &y& Elsevier]

Quetiapine (QUE) and repetitive transcranial magnetic stimulation (rTMS) have been considered to be possible monotherapies for depression or adjunctive therapies for the treatment of the resistant depression, but the underlying mechanisms remain unclear. The present study aimed to assess the effects of combined QUE and rTMS treatment on depressive-like behaviors, hippocampal proliferation, and the in vivo and in vitro expressions of phosphorylated extracellular signal-regulated protein kinase (pERK1/2) and brain-derived neurotrophic factor (BDNF) in male Sprague–Dawley rats. The administration of QUE and rTMS was determined not only to reverse the depressive-like behaviors of rats exposed to chronic unpredictable stress (CUS) but also to restore the protein expressions of pERK1/2 and BDNF and cell proliferation in the hippocampus. Additionally, QUE and rTMS promoted the proliferation and increased the expression of pERK1/2 and BDNF in hippocampal-derived neural stem cells (NSCs), and these effects were abolished by U0126. Taken together, these results suggest that the antidepressive-like effects of QUE and rTMS might be related to the activation of the BDNF/ERK signaling pathway and the up-regulation of cell proliferation in the hippocampus. [ABSTRACT FROM AUTHOR]