Experimental Physiopathology Laboratory, Postgraduation Program in Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Braz J Psychiatry. 2009 Sep;31(3):247-52. doi: 10.1590/s1516-44462009000300010.
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.
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.
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.
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.
临床发现氯胺酮可能可用于治疗重度抑郁症。本研究旨在比较氯胺酮和丙咪嗪给药后大鼠特定脑区的行为效应和脑肌酸激酶活性。
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；测量不同脑区的肌酸激酶活性。
结果表明，与生理盐水组相比，氯胺酮（10 和 15mg/kg）和丙咪嗪（20 和 30mg/kg）降低了不动时间。我们还观察到，氯胺酮（10 和 15mg/kg）和丙咪嗪（20 和 30mg/kg）增加了纹状体和大脑皮层的肌酸激酶活性。氯胺酮最高剂量（15mg/kg）和丙咪嗪（20 和 30mg/kg）增加了小脑和前额叶皮层的肌酸激酶活性。另一方面，海马体没有受到影响。
鉴于代谢障碍可能与抑郁症的病理生理学有关，因此抗抑郁药对能量代谢的调节（如肌酸激酶活性的增加）可能是这些药物的重要作用机制。
