Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Brain Res Bull. 2010 May 31;82(3-4):224-7. doi: 10.1016/j.brainresbull.2010.03.006. Epub 2010 Mar 25.
Several works report brain impairment of metabolism as a mechanism underlying depression. Citrate synthase and succinate dehydrogenase are enzymes localized within cells in the mitochondrial matrix and are important steps of Krebs cycle. In addition, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase and succinate dehydrogenase activities from rat brain after chronic administration of paroxetine, nortriptiline and venlafaxine. Adult male Wistar rats received daily injections of paroxetine (10mg/kg), nortriptiline (15mg/kg), venlafaxine (10mg/kg) or saline in 1.0mL/kg volume for 15 days. Twelve hours after the last administration, the rats were killed by decapitation, the hippocampus, striatum and prefrontal cortex were immediately removed, and activities of citrate synthase and succinate dehydrogenase were measured. We verified that chronic administration of paroxetine increased citrate synthase activity in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected. Chronic administration of nortriptiline and venlafaxine did not affect the enzyme activity in these brain areas. Succinate dehydrogenase activity was increased by chronic administration of paroxetine and nortriptiline in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected either. Chronic administration of venlafaxine increased succinate dehydrogenase activity in prefrontal cortex, but did not affect the enzyme activity in cerebellum, hippocampus, striatum and cerebral cortex. Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, an increase in these enzymes by antidepressants may be an important mechanism of action of these drugs.
几项研究报告指出，代谢性脑损伤是抑郁症的发病机制之一。柠檬酸合酶和琥珀酸脱氢酶是定位于线粒体基质细胞内的酶，是三羧酸循环的重要步骤。此外，柠檬酸合酶已被用作存在完整线粒体的定量酶标志物。因此，我们研究了慢性给予帕罗西汀、去甲替林和文拉法辛后大鼠大脑中的柠檬酸合酶和琥珀酸脱氢酶活性。成年雄性 Wistar 大鼠每天接受帕罗西汀（10mg/kg）、去甲替林（15mg/kg）、文拉法辛（10mg/kg）或生理盐水（1.0mL/kg）注射 15 天。末次给药 12 小时后，大鼠断头处死，迅速取出海马体、纹状体和前额叶皮质，测定柠檬酸合酶和琥珀酸脱氢酶活性。我们验证了慢性给予帕罗西汀增加成年大鼠前额叶皮质、海马体、纹状体和大脑皮质中的柠檬酸合酶活性；而小脑不受影响。慢性给予去甲替林和文拉法辛不影响这些脑区的酶活性。慢性给予帕罗西汀和去甲替林可增加成年大鼠前额叶皮质、海马体、纹状体和大脑皮质中的琥珀酸脱氢酶活性；小脑也不受影响。慢性给予文拉法辛可增加前额叶皮质中的琥珀酸脱氢酶活性，但不影响小脑、海马体、纹状体和大脑皮质中的酶活性。鉴于代谢损伤可能与抑郁障碍的病理生理学有关，因此抗抑郁药增加这些酶的活性可能是这些药物的重要作用机制。
