不同剂量氯胺酮的抗抑郁作用及其与海马mTOR及GluR1的关系

被引:7
作者
余海鹰 [1 ]
高志勤 [1 ]
杨春 [1 ]
杨春 [2 ]
周志强 [2 ]
杨建军 [2 ]
机构
[1] 解放军第医院精神科
[2] 南京大学医学院临床学院 南京军区南京总医院麻醉科
关键词
氯胺酮; 抑郁; 雷帕霉素靶蛋白; 谷氨酸受体1; 强迫游泳实验;
D O I
暂无
中图分类号
R749.4 [情感性精神病];
学科分类号
100204 [神经病学];
摘要
目的探讨不同剂量氯胺酮对强迫游泳大鼠抗抑郁效应的影响及其潜在机制。方法40只2月龄雄性Wistar大鼠随机均分为4组(n=10),行强迫游泳实验(forced swimming test,FST)15 min以建立大鼠抑郁模型。次日,分别腹腔注射生理盐水、氯胺酮5 mg/kg、氯胺酮10 mg/kg、氯胺酮20 mg/kg。30 min后,行FST5 min并记录其不动时间。行为学测试后,取海马组织测定雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)及谷氨酸受体1(glutamate receptor 1,GluR1)的含量。结果氯胺酮5 mg/kg组、10 mg/kg组和20 mg/kg组大鼠强迫游泳不动时间分别为136±13 s、119±12 s和95±20 s,与对照组的169±12 s相比,各组氯胺酮大鼠强迫游泳不动时间明显减少且呈剂量依赖性,P<0.05;各组氯胺酮大鼠海马组织mTOR含量分别为1.52±0.19、2.36±0.13和2.95±0.22,较对照组的0.87±0.11显著增高,P<0.05;各组氯胺酮大鼠海马组织GluR1含量分别为1.23±0.11、1.45±0.06和1.60±0.13,亦较对照组的0.91±0.07显著增高,P<0.05。结论氯胺酮具有确切的抗抑郁作用,其机理可能与海马组织mTOR及GluR1的上调有关。
引用
收藏
页码:169 / 172
页数:4
相关论文
共 11 条
[1]
Monitoring Ketamine treatment Response in a Depressed Patient via Peripheral Mammalian target of Rapamycin Activation [J].
Denk, Magdalena C. ;
Rewerts, Christiane ;
Holsboer, Florian ;
Erhardt-Lehmann, Angelika ;
Turck, Christoph W. .
AMERICAN JOURNAL OF PSYCHIATRY, 2011, 168 (07) :751-752
[2]
Chronic antidepressant treatments induce a time-dependent up-regulation of AMPA receptor subunit protein levels [J].
Barbon, Alessandro ;
Caracciolo, Luca ;
Orlandi, Cesare ;
Musazzi, Laura ;
Mallei, Alessandra ;
La Via, Luca ;
Bonini, Daniela ;
Mora, Cristina ;
Tardito, Daniela ;
Gennarelli, Massimo ;
Racagni, Giorgio ;
Popoli, Maurizio ;
Barlati, Sergio .
NEUROCHEMISTRY INTERNATIONAL, 2011, 59 (06) :896-905
[3]
Glutamate-based antidepressants: 20 years on [J].
Skolnick, Phil ;
Popik, Piotr ;
Trullas, Ramon .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2009, 30 (11) :563-569
[4]
Ketamine and the next generation of antidepressants with a rapid onset of action [J].
Machado-Vieira, Rodrigo ;
Salvadore, Giacomo ;
DiazGranados, Nancy ;
Zarate, Carlos A., Jr. .
PHARMACOLOGY & THERAPEUTICS, 2009, 123 (02) :143-150
[5]
Mammalian target of rapamycin (mTOR) is involved in the neuronal differentiation of neural progenitors induced by insulin [J].
Han, Jin ;
Wang, Bin ;
Mao, Zhifeng ;
Gao, Yuan ;
Zhao, Yanhong ;
Zhang, Jing ;
Chen, Bing ;
Wang, Xia ;
Dai, Jianwu .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2008, 39 (01) :118-124
[6]
Cellular mechanisms underlying the antidepressant effects of ketamine:: Role of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors [J].
Maeng, Sungho ;
Zarate, Carlos A., Jr. ;
Du, Jing ;
Schloesser, Robert J. ;
McCammon, Joseph ;
Chen, Guang ;
Manji, Husseini K. .
BIOLOGICAL PSYCHIATRY, 2008, 63 (04) :349-352
[7]
Antidepressive-like effects of rapamycin in animal models: Implications for mTOR inhibition as a new target for treatment of affective disorders [J].
Cleary, C. ;
Linde, J. A. S. ;
Hiscock, K. M. ;
Hadas, I. ;
Belmaker, R. H. ;
Agam, G. ;
Flaisher-Grinberg, S. ;
Einat, H. .
BRAIN RESEARCH BULLETIN, 2008, 76 (05) :469-473
[8]
A phenotypic small-molecule screen identifies an orphan ligand-receptor pair that regulates neural stem cell differentiation [J].
Saxe, Jonathan P. ;
Wu, Hao ;
Kelly, Theresa K. ;
Phelps, Michael E. ;
Sun, Yi E. ;
Kornblum, Harley I. ;
Huang, Jing .
CHEMISTRY & BIOLOGY, 2007, 14 (09) :1019-1030
[9]
Antidepressant-like actions of an AMPA receptor potentiator (LY392098) [J].
Li, X ;
Tizzano, JP ;
Griffey, K ;
Clay, M ;
Lindstrom, T ;
Skolnick, P .
NEUROPHARMACOLOGY, 2001, 40 (08) :1028-1033
[10]
不同剂量氯胺酮对抑郁大鼠海马脑源性神经营养因子和酪氨酸受体激酶B的影响 [J].
杨春 ;
李文媛 ;
张广芬 ;
徐世霞 ;
周志强 ;
杨建军 ;
徐建国 .
中华麻醉学杂志, 2011, (04)