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Title: Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons
Author: Ye, Zeng-You ; Lu, Yun-Gang ; Sun, Hao ; Cheng, Xin-Ping ; Xu, Tian-Le(徐天乐) ; Zhou, Jiang-Ning
Source: BRAIN RESEARCH
Issued Date: 2008
Volume: 1239, Issue:pt 1, Pages:77-84
Keyword: Antidepressant ; Fluoxetine-associated seizure ; Whole-cell patch-clamp ; Hippocampus ; Competitive inhibition ; Subtype-selectivity ; DORSAL-HORN NEURONS ; IN-VITRO ; SEIZURE ; ANTIDEPRESSANTS ; THERAPY ; BINDING ; SLICES ; NEUROSTEROIDS ; EXCITATION ; CHANNELS
Subject: Neurosciences & Neurology
Corresponding Author: Zhou, JN (reprint author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China,zyye@mail.ustc.edu.cn
English Abstract: Fluoxetine is a selective serotonin reuptake inhibitor widely used for treating depression. However, fluoxetine treatment may lead to seizures at higher doses, which underlying mechanism remains largely unknown. In this study, we examined the effects of fluoxetine on glycine receptor (GlyR) activity. Using the whole-cell patch-clamp recording method, we found that fluoxetine and its metabolite norfluoxetine inhibited glycine-induced currents in cultured rat hippocampal neurons. This inhibition was dose-dependent, and voltage-independent. Fluoxetine shifted the glycine concentration-response curve to the right without altering the maximal current. Both Lineweaver-Burk and Schild plots suggest competitive inhibition. The amount of fluoxetine inhibition significantly increased when homomeric GlyRs were selectively inhibited with picrotoxin. Moreover, fluoxetine inhibited the current mediated by heteromeric alpha 2 beta- but not homomeric alpha 2-GlyRs transiently expressed in HEK293T cells. These results suggest that fluoxetine is a competitive and subtype-selective GlyR inhibitor, which may explain its capacity to induce seizures. (C) 2008 Elsevier B.V. All rights reserved.
Indexed Type: SCI
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1692
Appears in Collections:神经所(总)_期刊论文

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Recommended Citation:
Ye, Zeng-You; Lu, Yun-Gang; Sun, Hao; Cheng, Xin-Ping; Xu, Tian-Le; Zhou, Jiang-Ning.Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons,BRAIN RESEARCH,2008,1239():77-84
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