Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Pharmacol Biochem Behav. 2022 Sep;219:173434. doi: 10.1016/j.pbb.2022.173434. Epub 2022 Jul 25.
A previous study from our Laboratory showed no alteration in inflammatory parameters seven days after ouabain (OUA) administration, a NaKATPase inhibitor, which was previously considered only a mania model. However, the administration of OUA in rats was recently validated as a model of bipolar disorder (BD) symptoms, demonstrating that 14 days after single intracerebroventricular (ICV) administration, OUA also induces depressive-like behavior. Therefore, it is important to investigate the long-term effect of OUA on inflammatory parameters since this mechanism seems to play a key role in BD physiopathology.
Adult male Wistar rats received a single ICV administration of OUA or artificial cerebrospinal fluid (aCSF). From the fourth day after the ICV infusion, the rats received saline or Lithium (Li) for 14 days. The open-field test was performed on the 7th day after OUA. On the 14th day, locomotion was re-evaluated, and the forced swimming test (FST) was used to evaluate depressive-like behavior. Inflammatory parameters were assessed in the frontal cortex and hippocampus.
OUA increased the locomotion of rats after seven days, considered a mania-like behavior. In the FST, OUA increased the time of immobility on the 14th day, considered a depressive-like behavior. Li reversed the mania-like behavior and partially reversed the depressive-like behavior. Furthermore, OUA increased the levels of interleukin (IL)-1β, IL-6, IL-10, TNF-α, and CINC-1 in the frontal cortex and hippocampus. Li treatment reverses all these inflammatory alterations.
This study suggests that the long-term NaKATPase inhibition effects induce depressive-like behavior, which was accompanied by inflammation in the BD symptoms model.
本实验室之前的一项研究表明，在给予 Na+/K+-ATP 酶抑制剂哇巴因（OUA）七天后，炎症参数没有改变，而 OUA 之前仅被认为是躁狂症模型。然而，最近有研究表明，OUA 对大鼠的给药可验证为双相障碍（BD）症状模型，表明在单次侧脑室（ICV）给药 14 天后，OUA 还会引起类似抑郁的行为。因此，研究 OUA 对炎症参数的长期影响很重要，因为这种机制似乎在 BD 病理生理学中起着关键作用。
成年雄性 Wistar 大鼠接受单次 ICV 哇巴因或人工脑脊液（aCSF）给药。在 ICV 输注后的第四天，大鼠接受生理盐水或锂（Li）治疗 14 天。在 OUA 给药后第七天进行旷场试验。在第 14 天，重新评估运动能力，并使用强迫游泳试验（FST）评估类似抑郁的行为。在额叶皮质和海马中评估炎症参数。
OUA 在七天后增加了大鼠的运动能力，被认为是躁狂样行为。在 FST 中，OUA 在第 14 天增加了不动时间，被认为是类似抑郁的行为。Li 逆转了躁狂样行为并部分逆转了类似抑郁的行为。此外，OUA 增加了额叶皮质和海马中白细胞介素（IL）-1β、IL-6、IL-10、TNF-α 和 CINC-1 的水平。Li 处理逆转了所有这些炎症改变。
本研究表明，长期的 Na+/K+-ATP 酶抑制作用会导致类似抑郁的行为，这伴随着 BD 症状模型中的炎症。
