Division of Molecular Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.
J Psychopharmacol. 2010 Dec;24(12):1772-8. doi: 10.1177/0269881109359102. Epub 2010 Feb 1.
The anticonvulsant drug lamotrigine has been shown to produce strong antidepressant effects in the treatment of patients with bipolar disorder. However, to date there are few preclinical reports on its behavioral actions in animal models of depression or its underlying molecular mechanisms. The current study investigated the effects of lamotrigine in the forced swimming test and the learned helplessness test. The results demonstrate that both 15 and 30 mg/kg acute treatment of lamotrigine significantly reduced immobility in the forced swimming test without affecting locomotor activity. Sub-chronic twice daily injections of 30 mg/kg lamotrigine robustly decreased escape failures in animals that had developed learned helplessness symptoms. In parallel, the sub-chronic lamotrigine treatment also up-regulated frontal and hippocampal brain-derived neurotrophic factor expression in both naive and stressed animals and restored the stress-induced down-regulation of brain-derived neurotrophic factor expression. This study provides further evidence for the use of lamotrigine as a novel antidepressant in the treatment of bipolar disorders.
抗惊厥药物拉莫三嗪已被证明在治疗双相情感障碍患者时具有很强的抗抑郁作用。然而，迄今为止，关于其在抑郁动物模型中的行为作用及其潜在的分子机制的临床前报告很少。本研究调查了拉莫三嗪在强迫游泳试验和习得性无助试验中的作用。结果表明，急性给予 15 和 30mg/kg 的拉莫三嗪均可显著减少强迫游泳试验中的不动时间，而不影响运动活性。每日两次给予 30mg/kg 的拉莫三嗪亚慢性治疗可显著减少出现习得性无助症状的动物的逃避失败。平行地，拉莫三嗪的亚慢性治疗还上调了未受应激和应激动物的额叶和海马脑源性神经营养因子表达，并恢复了应激诱导的脑源性神经营养因子表达下调。本研究为将拉莫三嗪作为一种新型抗抑郁药用于治疗双相情感障碍提供了进一步的证据。
