Rapid acting antidepressant-like effects of acetyl-L-carnitine mediated by PI3K/AKT/BDNF/VGF signali

• 作 者: ChuangWang;YangLu;PeipeiLin;TonghePan;ZhanchengXue;QinwenWang;WenhuaZhou;JunfangZhang;
• 机 构: Zhejiang Provincial Key Laboratory of Pathophysiology,Department of Physiology and Pharmacology,Scho
• 出 处: Symposium for Chinese Neuroscientists Worldwide 2014(第八届海内外华
• 发表日期: 2014年期

　　The possible involvement of the PI3K/AKT/BDNF/VGF signaling in rapid acting antidepressive-like effects of antidepressant has been explored by progressively more studies.However,whether this signaling participates in the antidepressant-like effects of acetyl-L-carnitine(ALC)has not been examined.Herein,we assessed the antidepressant effects of ALC using the forced swimming test(FST)and chronic unpredictable mild stress(CUMS)paradigm.Acute administration of ALC(5,25,50 and 100 mg/kg,i.p.)dose-dependently produced antidepressant-like effects on behavior in mice.ALC(100 mg/kg,i.p.)also reversed depressant-like behavior and the downregulation of p-AKT,BDNF and VGF in hippocampus and prefrontal cortex of mice induced by CUMS.In addition,intracerebroventricular(i.c.v.)infusions of LY294002(10 nmol/side),a specific phosphatidylinositol 3-kinase(PI3K)inhibitor,significantly prevented the antidepressant-like effect of ALC(100 mg/kg,i.p.).Furthermore,our results demonstrated that ALC exerted rapid acting antidepressant-like effects that might be mediated by the PI3K/Akt/BDNF/VGF signaling pathway.