Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
Pharmacol Rep. 2017 Oct;69(5):1094-1102. doi: 10.1016/j.pharep.2017.04.021. Epub 2017 May 6.
Major depressive disorder (MDD) affects many people in the world. However, around 40% of patients do not respond to any pharmacological drugs. An alternative is to use a combination of different pharmacological groups or the combination of a classical antidepressant with a substance that can potentiate its effect. Thus, this study aimed to investigate the synergistic interactions between different antidepressants, including fluoxetine, quetiapine and lamotrigine in combination with ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist.
Wistar rats were acutely treated with fluoxetine (1.25mg/kg), quetiapine (5mg/kg), and lamotrigine (5.0mg/kg) alone or in combination with ketamine (5.0mg/kg), and then subjected to behavioral tests. In addition, oxidative damage and antioxidant capacity were assessed in the rat brain, and pro-inflammatory cytokines levels were evaluated in the serum.
It was observed a synergistic effect of ketamine in combination with fluoxetine on the immobility time in the forced swimming test, indicating an antidepressant effect. Other antidepressant did not show effects when administrated alone or joint to ketamine. The combination of ketamine with other antidepressants, particularly quetiapine, in some brain regions induced an increase in damage to lipids and proteins. However, the combination of ketamine with fluoxetine increased the antioxidant activity of superoxide dismutase, and decreased oxidative damage, thus suggesting a neuroprotective effect of the combination of these drugs. The combination of ketamine with fluoxetine or lamotrigine reduced pro-inflammatory cytokines levels.
In conclusion, ketamine induced antioxidant or pro-antioxidant effects dependent of antidepressant classes or brain area.
重度抑郁症（MDD）影响着全世界许多人。然而，约有 40%的患者对任何药物都没有反应。另一种方法是使用不同药物组合或将经典抗抑郁药与可增强其效果的物质联合使用。因此，本研究旨在研究不同抗抑郁药（包括氟西汀、喹硫平和拉莫三嗪）与 NMDA 受体拮抗剂氯胺酮联合使用的协同作用。
Wistar 大鼠急性给予氟西汀（1.25mg/kg）、喹硫平（5mg/kg）和拉莫三嗪（5.0mg/kg）单独或与氯胺酮（5.0mg/kg）联合用药，然后进行行为测试。此外，评估了大鼠大脑中的氧化损伤和抗氧化能力，以及血清中的促炎细胞因子水平。
观察到氯胺酮与氟西汀联合使用对强迫游泳试验中不动时间的协同作用，表明具有抗抑郁作用。其他抗抑郁药单独或联合氯胺酮使用均无作用。氯胺酮与其他抗抑郁药（特别是喹硫平）联合使用，特别是在一些脑区，会导致脂质和蛋白质损伤增加。然而，氯胺酮与氟西汀联合使用增加了超氧化物歧化酶的抗氧化活性，减少了氧化损伤，从而表明这些药物联合使用具有神经保护作用。氯胺酮与氟西汀或拉莫三嗪联合使用可降低促炎细胞因子水平。
总之，氯胺酮诱导的抗氧化或促抗氧化作用取决于抗抑郁药类别或脑区。
