Department of Biochemistry, Centre of Biological Sciences, Federal University of Santa Catarina, Campus Universitario, Trindade, Florianopolis, Santa Catarina, Brazil.
Bipolar Disord. 2010 Jun;12(4):414-24. doi: 10.1111/j.1399-5618.2010.00827.x.
Bipolar disorder (BD) is a chronic, prevalent, and highly debilitating psychiatric illness. Folic acid has been shown to have antidepressant-like effects in preclinical and clinical studies and has also been suggested to play a role in BD. The present work investigates the therapeutic value of folic acid supplementation in a preclinical animal model of mania induced by ouabain.
Male Wistar rats were treated twice daily for seven days with folic acid (10, 50, and 100 mg/kg, p.o.) or the mood stabilizer lithium chloride (LiCl) (45 mg/kg, p.o.). One day after the last dose was given, the animals received an i.c.v. injection of ouabain (10 microM), a Na(+),K(+)-ATPase-inhibiting compound. Locomotor activity was assessed in the open-field test. Thiobarbituric acid-reactive substance (TBARS) levels, glutathione peroxidase (GPx), and glutathione reductase (GR) activities were measured in the cerebral cortex and hippocampus.
Ouabain (10 microM, i.c.v.) significantly increased motor activity in the open-field test, and seven days of pretreatment with folic acid (50 mg/kg, p.o.) or LiCl (45 mg/kg, p.o.) completely prevented this effect. Ouabain treatment elicited lipid peroxidation (increased TBARS levels) and reduced GPx activity in the hippocampus. GR activity was decreased in the cerebral cortex and hippocampus. These effects were prevented by pretreatment with folic acid and LiCl.
Our results show that folic acid, similarly to LiCl, produces a clear antimanic action and prevents the neurochemical alterations indicative of oxidative stress in an animal model of mania.
双相情感障碍（BD）是一种慢性、普遍存在且高度致残的精神疾病。叶酸在临床前和临床研究中已显示出抗抑郁作用，并且还被认为在 BD 中发挥作用。本研究旨在探讨叶酸补充在哇巴因诱导的躁狂症动物模型中的治疗价值。
雄性 Wistar 大鼠每日两次接受叶酸（10、50 和 100mg/kg，口服）或心境稳定剂氯化锂（LiCl）（45mg/kg，口服）治疗 7 天。最后一次给药后一天，动物接受脑室注射哇巴因（10μM），一种 Na(+)，K(+)-ATP 酶抑制剂。在开阔场测试中评估运动活动。在大脑皮层和海马体中测量丙二醛（TBARS）水平、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）活性。
脑室注射哇巴因（10μM）显著增加了开阔场测试中的运动活动，而 7 天的叶酸（50mg/kg，口服）或 LiCl（45mg/kg，口服）预处理完全阻止了这种作用。哇巴因处理引起海马体脂质过氧化（TBARS 水平升高）和 GPx 活性降低。GR 活性在大脑皮层和海马体中降低。这些作用可通过叶酸和 LiCl 的预处理来预防。
我们的结果表明，叶酸与 LiCl 相似，具有明显的抗躁狂作用，并预防了躁狂症动物模型中提示氧化应激的神经化学改变。
