Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160 014, India.
Indian J Pharmacol. 2011 May;43(3):324-9. doi: 10.4103/0253-7613.81506.
The present study was designed to elucidate the possible nitric oxide (NO) mechanism in the protective effect of antidepressants using mice model of chronic fatigue syndrome (CFS).
Male albino laca mice were forced to swim for each 6 min session for 7 days and immobility period was measured on every alternate day (1(st), 3(rd), 5(th), 7(th)). After 7 days various behavioral tests (locomotor, mirror chamber, and plus maze tests for anxiety) were performed and biochemical estimations (lipid peroxidation, nitrite levels, GSH (reduced glutathione), and catalase activity) in mice brain were performed. Animals were pretreated with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) daily for 7 days.
The present study showed that continued forced swimming for 7 days caused chronic fatigue-induced anxiety-like behavior as assessed in mirror chamber, plus maze tests, and impairment in locomotor activity followed by oxidative damage (as evidenced by increased lipid peroxidation, nitrite levels, depleted reduced glutathione, and catalase activity) in animals. Seven days pretreatment with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) significantly improved behavioral and biochemical alterations. Further, L-nitro-arginine methyl ester (L-NAME,5 mg/kg) and methylene blue (MB, 10 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) potentiated their protective effect. However, l-arginine (100 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) reversed their protective effect as compared with their effect per se (P < 0.05).
The present study suggests that protective effect of citalopram and imipramine might be due to its NO modulation against chronic fatigue induced behavioral and biochemical alterations.
本研究旨在通过慢性疲劳综合征（CFS）小鼠模型阐明抗抑郁药的保护作用中可能的一氧化氮（NO）机制。
雄性白化 Laca 小鼠被强迫每 6 分钟游泳一次，共进行 7 天，隔天测量不动期（第 1、3、5、7 天）。7 天后，对小鼠进行各种行为测试（运动、镜像室和加迷宫测试焦虑）和生化评估（脂质过氧化、亚硝酸盐水平、GSH（还原型谷胱甘肽）和过氧化氢酶活性）。动物预先用西酞普兰（5 和 10mg/kg）和丙咪嗪（10 和 20mg/kg）每日处理 7 天。
本研究表明，连续 7 天强迫游泳导致慢性疲劳诱导的焦虑样行为，如在镜像室、加迷宫测试和运动活动受损后，动物的氧化损伤（表现为脂质过氧化增加、亚硝酸盐水平升高、还原型谷胱甘肽耗竭和过氧化氢酶活性降低）。西酞普兰（5 和 10mg/kg）和丙咪嗪（10 和 20mg/kg）预处理 7 天可显著改善行为和生化改变。此外，L-硝基精氨酸甲酯（L-NAME，5mg/kg）和亚甲蓝（MB，10mg/kg）预处理西酞普兰（5mg/kg）或丙咪嗪（10mg/kg）增强了其保护作用。然而，西酞普兰（5mg/kg）或丙咪嗪（10mg/kg）与 l-精氨酸（100mg/kg）预处理逆转了其保护作用，与它们自身的作用相比（P<0.05）。
本研究表明，西酞普兰和丙咪嗪的保护作用可能是由于其对慢性疲劳诱导的行为和生化改变的 NO 调节。
