Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats
Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats
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DOI：
10.1590/s1516-44462009000300010
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发表时间：
2009-09-01
影响因子：
5.5
通讯作者：
Streck, Emilio L.
中科院分区：
文献类型：
--
作者：
Assis, Lara C.;Rezin, Gislaine T.;Streck, Emilio L.
目的：临床研究提示氯胺酮可用于治疗抑郁症。本研究旨在比较氯胺酮和丙咪嗪给药后大鼠的行为学效应和特定脑区的脑肌酸激酶活性。方法：大鼠急性给予氯胺酮或丙咪嗪，通过强迫游泳试验评估抗抑郁样活性;测量脑不同区域的肌酸激酶活性。结果：氯胺酮（10、15mg/kg）和丙咪嗪（20、30mg/kg）组小鼠不动时间较生理盐水组明显缩短。氯胺酮（10和15mg/kg）和丙咪嗪（20和30mg/kg）可使纹状体和大脑皮层肌酸激酶活性增高。最高剂量的氯胺酮（15 mg/kg）和丙咪嗪（20和30 mg/kg）可增加小脑和前额皮质中的肌酸激酶活性。另一方面，海马体没有受到影响。结论：考虑到代谢障碍可能参与抑郁症的病理生理学，抗抑郁药对能量代谢的调节（如肌酸激酶活性增加）可能是这些药物的重要作用机制。
Objective: Clinical findings suggest that ketamine may be used for the treatment of major depression. The present study aimed to compare behavioral effects and brain Creatine kinase activity in specific brain regions after administration of ketamine and imipramine in rats. Method: Rats were acutely given ketamine or imipramine and antidepressant-like activity was assessed by the forced swimming test; Creatine kinase activity was measured in different regions of the brain. Results: The results showed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) reduced immobility time when compared to saline group. We also observed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in striatum and cerebral cortex. Ketamine at the highest dose (15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in cerebellum and prefrontal cortex. On the other hand, hippocampus was not affected. Conclusion: Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, the modulation of energy metabolism (like increase in Creatine kinase activity) by antidepressants could be an important mechanism of action of these drugs.