Up-regulation of gamma-aminobutyric acid transporter mediates ethanol sensitivity in mice
文献类型：期刊论文
| 作者 | Hu, JH; Ma, YH; Yang, N; Mei, ZT; Zhang, MH; Fei, J; Guo, LH |
| 刊名 | NEUROSCIENCE
 |
| 出版日期 | 2004 |
| 卷号 | 123期号:4页码:807-812 |
| 关键词 | GABA transporter GABA re-uptake inhibitor alcoholism transgenic mouse |
| 通讯作者 | Guo, LH (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,jfei@sibs.ac.cn ; mhzhang@sunm.shcnc.ac.cn |
| 英文摘要 | Ethanol is among the most widely abused drugs in the world. Chronic ethanol consumption leads to ethanol tolerance and addiction, and impairs learning and memory. Na+/Cl- dependent GABA transporters play an important role in controlling the concentration of GABA in the synaptic cleft, and thus they control the intensity and duration of synaptic transmission of GABA. It has been suggested that GABAergic system is involved in ethanol consumption, tolerance and addiction, because chronic ethanol consumption alters the expression of GABA(A) receptors and drugs on GABA receptors affect ethanol actions. The results of the present study reveal that that activity of GABA transporters in mouse brain after 15-min acute ethanol injection or after chronic ethanol consumption is increased. Moreover, mice pre-injected with a competitive or a noncompetitive antagonist of gamma-aminobutyric acid transporter subtype 1 (GAT1) showed high sensitivity to the sedative/hypnotic effects of ethanol. In contrast, transgenic mice overexpressing GAT1 displayed low sensitivity to ethanol, as shown by the righting reflex test. Mice overexpressing GAT1 survived a lethal dose of ethanol (9 g/kg, i.p.) longer, maintained locomotor activity longer after a sub-lethal dose (1.75 g/kg, i.p.) and exhibited a higher median lethal dose than wild-type littermates. These results suggest that GAT1 plays an important role in sensitivity to ethanol, and might be a therapeutic target for alcoholism prevention and treatment. Acute and chronic ethanol administration resulted in the increase of GABA transporter function. Use of GAT1 selective inhibitors and GAT1 overexpressing mice thus demonstrate that GAT1 should be an important protein mediating sensitivity to ethanol in mice. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. |
| 学科主题 | Neurosciences & Neurology |
| 类目[WOS] | Neurosciences |
| 关键词[WOS] | SUBTYPE-I LEADS ; RAT-BRAIN ; GABA TRANSPORTER ; TRANSGENIC MICE ; NEUROPEPTIDE-Y ; CONSUMPTION ; LOCALIZATION ; GLUTAMATE ; RECEPTORS ; OVEREXPRESSION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000188885600001 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2086]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Hu, JH,Ma, YH,Yang, N,et al. Up-regulation of gamma-aminobutyric acid transporter mediates ethanol sensitivity in mice[J]. NEUROSCIENCE,2004,123(4):807-812. |
| APA | Hu, JH.,Ma, YH.,Yang, N.,Mei, ZT.,Zhang, MH.,...&Guo, LH.(2004).Up-regulation of gamma-aminobutyric acid transporter mediates ethanol sensitivity in mice.NEUROSCIENCE,123(4),807-812. |
| MLA | Hu, JH,et al."Up-regulation of gamma-aminobutyric acid transporter mediates ethanol sensitivity in mice".NEUROSCIENCE 123.4(2004):807-812. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。