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Published on: May 14, 2018
Rapid-acting antidepressant-like effects of acetyl-l-carnitine mediated by PI3K/AKT/BDNF/VGF signaling pathway in
1Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, PR China; Department of Pharmacy, Henan Cancer Hospital, Zhengzhou 450008, PR China; Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
Abstract:
The possible involvement of the PI3K/AKT/BDNF/VGF signaling in rapid-acting antidepressant-like effects of antidepressants has been explored progressively by 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-like effects of ALC using the forced swimming test (FST). Our results demonstrated the dose-effect relationship of acute administration of ALC (5, 25, 50 and 100mg/kg, i.p.) and showed that it dose-dependently decreased the immobility time on FST of mice. In addition, ALC (100 mg/kg, i.p.) also reversed depressive-like behavior and the down-regulation of phosphorylated AKT (pAKT), brain-derived neurotrophic factor (BDNF) and neuropeptide VGF in the hippocampus and prefrontal cortex of mice induced by chronic unpredictable mild stress (CUMS) paradigm. Further, intra-cerebroventricular (i.c.v.) infusions of LY294002 (10 nmol/side), a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, significantly prevented the antidepressant-like effect of ALC (100mg/kg, i.p.). In conclusion, our results demonstrated that ALC exerts rapid-acting antidepressant-like effects that might be mediated by the PI3K/AKT/BDNF/VGF signaling pathway.
