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Effects of ketamine, imipramine, and their combination on depression-like behaviors in Wistar Kyoto rats
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- Author:
- No author available
- Journal Title:
- Acta Physiologica Sinica
- Issue:
- 1
- DOI:
- 10.13294/j.aps.2016.0013
- Key Word:
- 氯胺酮;丙咪嗪;抗抑郁;β钙/钙调素依赖蛋白激酶Ⅱ;谷氨酸受体1;缰核;前额叶皮质;ketamine;imipramine;anti-depressant;β form of calcium/calmodulin-dependent protein kinase type Ⅱ;glutamate receptor 1;habenula;prefrontal cortex
Abstract： 本文旨在研究氯胺酮、丙咪嗪或两者联合用药对Wistar Kyoto (WKY)大鼠抑郁样行为的治疗效果和机制.取6周龄Wistar大鼠作为正常对照,给同龄WKY大鼠(抑郁症模型)腹腔注氯胺酮(给药1周,停药1周)、丙咪嗪(给药2周)或氯胺酮联合丙咪嗪.行糖水偏好及强迫游泳实验观察各组大鼠抑郁样行为的变化,用Western blot检测大鼠缰核β钙/钙调素依赖蛋白激酶Ⅱ(βform of calcium/calmodulin-dependent protein kinase type Ⅱ,pCaMKⅡ)和膜谷氨酸受体1(glutamate receptor 1,GluR1)蛋白表达,以及前额叶皮质的膜GluR1蛋白表达.结果显示,与Wistar大鼠相比,WKY大鼠糖水偏好程度显著降低,强迫游泳实验中不动时间显著增加;单独氯胺酮治疗对WKY大鼠的抑郁样行为没有显著作用,而丙咪嗪或氯胺酮联合丙咪嗪治疗可显著减少WKY大鼠不动时间.与Wistar大鼠相比,WKY大鼠缰核pCaMKII和膜GluR1蛋白表达显著上调,前额叶皮质的膜GluR1蛋白表达显著下调;单独氯胺酮治疗对WKY大鼠缰核βCaMKII和膜GluR1蛋白表达没有显著作用,但可上调前额叶皮质的膜GluR1蛋白表达;丙咪嗪或氯胺酮联合丙咪嗪治疗均可显著下调WKY大鼠缰核pCaMKⅡ和膜GluR1蛋白表达,上调前额叶皮质的膜GluR1蛋白表达,丙咪嗪对上述蛋白表达的作用和联合用药之间无显著差异.以上结果提示,丙咪嗪治疗2周显著改善了WKY大鼠的抑郁样行为,联合使用氯胺酮不能增强丙咪嗪的疗效;丙咪嗪的抗抑郁机制可能与缰核中βCaMKⅡ及膜GluR1表达下调以及前额叶皮质的膜GluR1表达上调有关.
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