Nicotine, but not mecamylamine, enhances antidepressant-like effects of citalopram and reboxetine in the mouse forced swim and tail suspension tests
Nicotine, but not mecamylamine, enhances antidepressant-like effects of citalopram and reboxetine in the mouse forced swim and tail suspension tests
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DOI：
10.1016/j.bbr.2008.08.016
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发表时间：
2009-01-30
影响因子：
2.7
通讯作者：
Redrobe, John P.
中科院分区：
文献类型：
--
作者：
Andreasen, Jesper T.;Redrobe, John P.
目前的文献表明烟碱乙酰胆碱受体（nAChR）与重度抑郁症有关。在啮齿类动物中，尼古丁和非选择性 nAChR 拮抗剂美加明都有类似抗抑郁作用的报道。尼古丁增加血清素能和去甲肾上腺素能神经元活性，并促进血清素和去甲肾上腺素的释放。因此，我们假设尼古丁可能增强血清素（例如西酞普兰）和/或去甲肾上腺素（例如瑞波西汀）再摄取抑制剂的行为效应。在这里，我们在小鼠强迫游泳试验（mFST）和小鼠悬尾试验（mTST）中测试尼古丁是否增强西酞普兰或瑞波西汀的活性。还研究了美加明增强抗抑郁药物作用的潜力。单独测试西酞普兰（3 和 10 mg/kg）或瑞波西汀（3、10 和 20 mg/kg）的亚阈值和阈值剂量，以及与尼古丁（0.3 和 1.0 mg/kg）和美加明（1 和 3 mg/kg）联合测试。进行运动活动实验以排除非特异性刺激作用。尼古丁 (1.0 mg/kg) 增强了 10 mg/kg 西酞普兰和 20 mg/kg 瑞波西汀在 mFST 中的作用。类似地，尼古丁（1.0 mg/kg）增强了 mTST 中 3 和 10 mg/kg 西酞普兰以及 3 和 10 mg/kg 瑞波西汀的作用。在测试的剂量组合中没有观察到伴随的运动刺激。美加明在某些测试中单独有效，但在测试剂量下并不能增强西酞普兰或瑞波西汀的作用。数据显示，尼古丁增强了血清素和去甲肾上腺素再摄取抑制剂的作用，可能反映了尼古丁对这两种神经递质释放的促进作用，并表明尼古丁可能增强抗抑郁作用。 (C) 2008 Elsevier B.V. 保留所有权利。
Current literature suggests that nicotinic acetylcholine receptors (nAChRs) are involved in major depression. In rodents, antidepressant-like effects of both nicotine and the non-selective nAChR antagonist mecamylamine have been reported. Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. Thus, we hypothesise that nicotine may enhance the behavioural effects of serotonin (e.g., citalopram) and/or noradrenaline (e.g., reboxetine) reuptake inhibitors. Here, we tested if nicotine enhanced the activity of citalopram or reboxetine in the mouse forced swim test (mFST) and the mouse tail suspension test (mTST). The potential for mecamylamine to augment antidepressant drug action was also investigated. Sub-threshold and threshold doses of citalopram (3 and 10 mg/kg) or reboxetine (3, 10 and 20 mg/kg) were tested alone and in combination with nicotine (0.3 and 1.0 mg/kg) and mecamylamine (1 and 3 mg/kg). Locomotor activity experiments were performed to rule out non-specific stimulant effects. Nicotine (1.0 mg/kg) enhanced the effect of 10 mg/kg citalopram and 20 mg/kg reboxetine in the mFST. Similarly, nicotine (1.0 mg/kg) enhanced the effect of 3 and 10 mg/kg citalopram and 3 and 10 mg/kg reboxetine in the mTST. No concomitant locomotor stimulation was observed at the tested dose combinations. Mecamylamine was effective on its own in some tests, but did not augment the effects of citalopram or reboxetine at the doses tested. The data show that nicotine enhances the effects of both serotonin and noradrenaline reuptake inhibitors, possibly reflecting nicotine's facilitating effects on the release of these two neurotransmitters, and indicating that nicotine may enhance antidepressant action. (C) 2008 Elsevier B.V. All rights reserved.