乙醇处理大鼠下丘脑和纹状体中5-羟色胺（2A）受体状态增强。
Enhanced 5-HT(2A) receptor status in the hypothalamus and corpus striatum of ethanol-treated rats.
作者信息
Akash K G, Balarama K S, Paulose C S
机构信息
Molecular neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682022 Kerala, India.
出版信息
Cell Mol Neurobiol. 2008 Nov;28(7):1017-25. doi: 10.1007/s10571-008-9281-2. Epub 2008 Apr 19.
AIM
Brain is the major target for the actions of ethanol and it can affect the brain in a variety of ways. In the present study we have investigated the changes in 5-HT level and the 5-HT(2A) receptors in the ethanol-treated rats.
METHODS
Wistar adult male rats of 180-200 g body weight were given free access to 15% (v/v) (approx.7.5 g/Kg body wt./day) ethanol for 15 days. Controls were given free access to water for 15 days. Brain 5-HT and its metabolites were assayed by high performance liquid chromatography (HPLC) integrated with an electrochemical detector (ECD) fitted with C-18-CLS-ODS reverse phase column. 5-HT(2A) receptor binding assay was done with different concentrations of [3H] MDL 100907.
RESULTS
The hypothalamic 5-HT content significantly increased (P < 0.001) with a decreased (P < 0.001) 5-HIAA/5-HT turnover in the ethanol-treated rats when compared to control. The corpus striatum 5-HT content significantly decreased (P < 0.01) with increased (P < 0.01) 5-HIAA/5- HT turnovers in the ethanol-treated rats when compared to control. Scatchard analysis of [(3)H] MDL 100907 against ketanserin in hypothalamus showed a significant increase (P < 0.001) in B(max )with a decreased affinity (P < 0.001) in ethanol-treated rats when compared to control. The competition curve for [3H] MDL 100907 against ketanserin fitted one-site model in all the groups with unity as Hill slope value. An increased K(i) and log (EC(50)) value were also observed in ethanol-treated rats when compared to control. Scatchard analysis of [3H] MDL 100907 against ketanserin in the corpus striatum of ethanol-treated rats showed a significant increase (P < 0.001) in B(max) and in affinity (P < 0.01) when compared to control. The change in affinity of the receptor protein in both corpus striatum and hypothalamus shows an altered receptor. The competition curve for [(3)H] MDL 100907 against ketanserin fitted one-site model in all the groups with unity as Hill slope value. There was no significant change in K(i) and log (EC (50)) value in ethanol-treated rats when compared to control.
CONCLUSION
The present study demonstrated the enhanced 5-HT(2A) receptor status in hypothalamus and corpus striatum. The ethanol-induced enhanced 5-HT(2A) receptors in the hypothalamus and corpus striatum has clinical significance in the better management of ethanol addiction. This will have therapeutic application.
目的
脑是乙醇作用的主要靶点，乙醇可通过多种方式影响脑。在本研究中，我们调查了乙醇处理大鼠中5-羟色胺（5-HT）水平及5-HT（2A）受体的变化。
方法
体重180 - 200 g的成年雄性Wistar大鼠自由饮用15%（v/v）（约7.5 g/千克体重/天）乙醇，持续15天。对照组大鼠自由饮水15天。采用配备C-18-CLS-ODS反相柱的高效液相色谱（HPLC）结合电化学检测器（ECD）测定脑内5-HT及其代谢产物。用不同浓度的[3H] MDL 100907进行5-HT（2A）受体结合试验。
结果
与对照组相比，乙醇处理大鼠下丘脑5-HT含量显著增加（P < 0.001），5-羟吲哚乙酸（5-HIAA）/5-HT周转率降低（P < 0.001）。与对照组相比，乙醇处理大鼠纹状体5-HT含量显著降低（P < 0.01），5-HIAA/5-HT周转率升高（P < 0.01）。对下丘脑[（3）H] MDL 100907与酮色林进行Scatchard分析显示，与对照组相比，乙醇处理大鼠的最大结合容量（B(max)）显著增加（P < 0.001），亲和力降低（P < 0.001）。所有组中[3H] MDL 100907与酮色林的竞争曲线均符合单点模型，Hill斜率值为1。与对照组相比，乙醇处理大鼠的抑制常数（K(i)）和半数有效浓度对数（log (EC(50))）值也升高。对乙醇处理大鼠纹状体中[3H] MDL 100907与酮色林进行Scatchard分析显示，与对照组相比，B(max)显著增加（P < 0.001），亲和力增加（P < 0.01）。纹状体和下丘脑受体蛋白亲和力的变化表明受体发生了改变。所有组中[（3）H] MDL 100907与酮色林的竞争曲线均符合单点模型，Hill斜率值为1。与对照组相比，乙醇处理大鼠的K(i)和log (EC (50))值无显著变化。
结论
本研究证明下丘脑和纹状体中5-HT（2A）受体状态增强。乙醇诱导的下丘脑和纹状体中5-HT（2A）受体增强在乙醇成瘾的更好管理方面具有临床意义。这将具有治疗应用价值。
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