Dhir Ashish, Kulkarni S K
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Pharmacol Biochem Behav. 2008 Jun;89(4):563-71. doi: 10.1016/j.pbb.2008.02.011. Epub 2008 Feb 12.
A state of chronic fatigue was produced in mice by subjecting them to forced swim inside a rectangular jar of specific dimensions everyday for a 6 min session for 15 days. Immobility period was recorded on alternate days. The effect of venlafaxine, a dual reuptake inhibitor of serotonin and norepinephrine was evaluated in this murine model of chronic fatigue. Venlafaxine was administered daily and on the days of testing, it was injected 30 min before forced swim session. On the 16th day i.e. 24 h after the last dose of venlafaxine, various behavioral, biochemical and neurotransmitter estimations in the brain were carried out. There was a significant increase in immobility period in vehicle treated mice on successive days, the maximum immobility score reaching on the 7th day and sustained till 15th day. Behavioral parameters revealed hyperlocomotion, anxiety response, muscle incoordination, hyperalgesia and memory deficit. Biochemical analysis showed a significant increase in lipid peroxidation, nitrite and myeloperoxidase levels and a decrease in the reduced glutathione (GSH) levels in brain homogenates. Further, there was a decrease in adrenal ascorbic acid following chronic forced swim. The neurotransmitter estimations in the brain samples revealed a decrease in norepinephrine, serotonin and dopamine levels on chronic exposure to forced swim for 15 days. Daily treatment with venlafaxine (8 and 16 mg/kg, i.p.) for 15 days produced a significant reduction in immobility period and reversed various behavioral, biochemical and neurotransmitter alterations induced by chronic fatigue. Venlafaxine could be of therapeutic potential in the treatment of chronic fatigue.
通过每天将小鼠置于特定尺寸的矩形玻璃罐中进行6分钟的强迫游泳，持续15天，从而在小鼠中诱发慢性疲劳状态。每隔一天记录静止时间。在这个慢性疲劳小鼠模型中评估了文拉法辛（一种血清素和去甲肾上腺素双重再摄取抑制剂）的效果。每天给予文拉法辛，在测试当天，在强迫游泳前30分钟注射。在第16天，即最后一剂文拉法辛给药24小时后，对大脑进行各种行为、生化和神经递质评估。在连续几天中，给予赋形剂处理的小鼠的静止时间显著增加，最大静止评分在第7天达到，并持续到第15天。行为参数显示活动亢进、焦虑反应、肌肉不协调、痛觉过敏和记忆缺陷。生化分析表明，脑匀浆中的脂质过氧化、亚硝酸盐和髓过氧化物酶水平显著增加，还原型谷胱甘肽（GSH）水平降低。此外，慢性强迫游泳后肾上腺抗坏血酸减少。对脑样本的神经递质评估显示，在慢性强迫游泳15天后，去甲肾上腺素、血清素和多巴胺水平降低。每天用文拉法辛（8和16毫克/千克，腹腔注射）治疗15天，可显著缩短静止时间，并逆转慢性疲劳引起的各种行为、生化和神经递质改变。文拉法辛在治疗慢性疲劳方面可能具有治疗潜力。
