PMID- 29274366 OWN - NLM STAT- MEDLINE DCOM- 20181113 LR - 20220331 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 131 DP - 2018 Mar 15 TI - Vesicular glutamate transporter 1 (VGLUT1)-mediated glutamate release and membrane GluA1 activation is involved in the rapid antidepressant-like effects of scopolamine in mice. PG - 209-222 LID - S0028-3908(17)30625-1 [pii] LID - 10.1016/j.neuropharm.2017.12.028 [doi] AB - Emerging data have identified certain drugs such as scopolamine as rapidly acting antidepressants for major depressive disorder (MDD) that increase glutamate release and induce neurotrophic factors through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation in rodent models. However, little research has addressed the direct mechanisms of scopolamine on AMPAR activation or vesicular glutamate transporter 1 (VGLUT1)-mediated glutamate release in the prefrontal cortex (PFC) of mice. Herein, using a chronic unpredictable stress (CUS) paradigm, acute treatment with scopolamine rapidly reversed stress-induced depression-like behaviors in mice. Our results showed that CUS-induced depression-like behaviors, accompanied by a decrease in membrane AMPAR subunit 1 (GluA1), phosphorylated GluA1 Ser845 (pGluA1 Ser845), brain-derived neurotrophic factor (BDNF) and VGF (non-acronymic) and an increase in bicaudal C homolog 1 gene (BICC1) in the PFC of mice, and these biochemical and behavioral abnormalities were ameliorated by acute scopolamine treatments. However, pharmacological block of AMPAR by NBQX infusion into the PFC significantly abolished these effects of scopolamine. In addition, knock down of VGLUT1 by lentiviral-mediated RNA interference in the PFC of mice was sufficient to induce depression-like phenotype, to decrease extracellular glutamate accumulation and to cause similar molecular changes with CUS in mice. Remarkably, VGLUT1 knockdown alleviated the rapid antidepressant-like actions of scopolamine and the effects of scopolamine on membrane GluA1-mediated BDNF, VGF and BICC1 changes. Altogether, our findings suggest that VGLUT1-mediated glutamate release and membrane GluA1 activation may play a critical role in the rapid-acting antidepressant-like effects of scopolamine in mice. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Yu, Hanjie AU - Yu H AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China. FAU - Li, Mengmeng AU - Li M AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China. FAU - Zhou, Dongsheng AU - Zhou D AD - Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, China. FAU - Lv, Dan AU - Lv D AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China. FAU - Liao, Qi AU - Liao Q AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China. FAU - Lou, Zhongze AU - Lou Z AD - Department of Psychosomatic Medicine, Ningbo First Hospital, 59 Liuting Str., Ningbo, Zhejiang 315010, China. FAU - Shen, Mengxin AU - Shen M AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China. FAU - Wang, Zhen AU - Wang Z AD - CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. FAU - Li, Ming AU - Li M AD - Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, 32 East Jiao-Chang Rd, Kunming, Yunnan 650223, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China. FAU - Xiao, Xiao AU - Xiao X AD - Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, 32 East Jiao-Chang Rd, Kunming, Yunnan 650223, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China. FAU - Zhang, Yanhua AU - Zhang Y AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China. FAU - Wang, Chuang AU - Wang C AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, China. Electronic address: wanglovechuang@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171220 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Antidepressive Agents) RN - 0 (Cholinergic Antagonists) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Receptors, AMPA) RN - 0 (Vesicular Glutamate Transport Protein 1) RN - 3KX376GY7L (Glutamic Acid) RN - DL48G20X8X (Scopolamine) RN - FST467XS7D (Saccharin) RN - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1) SB - IM MH - Animals MH - Antidepressive Agents/pharmacology/*therapeutic use MH - Cholinergic Antagonists/pharmacology/*therapeutic use MH - Depression/*drug therapy/etiology MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Fasting/adverse effects MH - Feeding Behavior/drug effects MH - Food Preferences/drug effects MH - Glutamic Acid/metabolism MH - Humans MH - Intercellular Signaling Peptides and Proteins/metabolism MH - Locomotion/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Prefrontal Cortex/drug effects/metabolism MH - Receptors, AMPA/*metabolism MH - Saccharin/administration & dosage MH - Scopolamine/pharmacology/*therapeutic use MH - Social Behavior MH - Stress, Psychological/complications MH - Swimming/psychology MH - Vesicular Glutamate Transport Protein 1/*metabolism MH - Water Deprivation OTO - NOTNLM OT - Bicaudal C homolog 1 gene (BICC1) OT - Brain-derived neurotrophic factor (BDNF) OT - Scopolamine OT - VGF (non-acronymic) OT - Vesicular glutamate transporter 1 (VGLUT1) OT - alpha-Amino-3-Hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) EDAT- 2017/12/24 06:00 MHDA- 2018/11/14 06:00 CRDT- 2017/12/24 06:00 PHST- 2017/09/23 00:00 [received] PHST- 2017/12/12 00:00 [revised] PHST- 2017/12/17 00:00 [accepted] PHST- 2017/12/24 06:00 [pubmed] PHST- 2018/11/14 06:00 [medline] PHST- 2017/12/24 06:00 [entrez] AID - S0028-3908(17)30625-1 [pii] AID - 10.1016/j.neuropharm.2017.12.028 [doi] PST - ppublish SO - Neuropharmacology. 2018 Mar 15;131:209-222. doi: 10.1016/j.neuropharm.2017.12.028. Epub 2017 Dec 20.