An Yan, Inoue Takeshi, Kitaichi Yuji, Nakagawa Shin, Wang Ce, Chen Chong, Song Ning, Kusumi Ichiro
Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
Eur J Pharmacol. 2015 Jan 15;747:13-7. doi: 10.1016/j.ejphar.2014.11.009. Epub 2014 Nov 29.
Lithium not only has a mood-stabilizing effect but also the augmentation effect of an antidepressant, the mechanism of which remains unclear. Although lithium may augment the effect of mirtazapine, this augmentation has not been confirmed. Using a contextual fear conditioning test in rats, an animal model of anxiety or fear, we examined the effect of subchronic lithium carbonate (in diet) in combination with systemic mirtazapine on the expression of contextual conditioned fear. Mirtazapine (10mg/kg) reduced freezing one day after fear conditioning dose-dependently, whereas the anxiolytic-like effect of mirtazapine (10mg/kg) diminished seven days after fear conditioning. When the interval between fear conditioning and testing was seven days, only the combination of subchronic 0.2% Li2CO3 but not 0.05% Li2CO3 with acute mirtazapine (10mg/kg) reduced freezing significantly. These results indicate that subchronic 0.2% Li2CO3 treatment enhanced the anxiolytic-like effect of systemic mirtazapine. This augmentation therapy might be useful for the treatment of anxiety disorders.
锂不仅具有情绪稳定作用，还具有抗抑郁药的增效作用，其机制尚不清楚。虽然锂可能增强米氮平的效果，但这种增效作用尚未得到证实。我们使用大鼠情境恐惧条件反射试验（一种焦虑或恐惧的动物模型），研究了亚慢性碳酸锂（添加到饮食中）与全身性米氮平联合使用对情境性条件恐惧表达的影响。恐惧条件反射后一天，米氮平（10mg/kg）剂量依赖性地减少了僵住反应，而恐惧条件反射后七天，米氮平（10mg/kg）的抗焦虑样作用减弱。当恐惧条件反射与测试之间的间隔为七天时，只有亚慢性0.2%碳酸锂与急性米氮平（10mg/kg）联合使用能显著减少僵住反应，而0.05%碳酸锂与急性米氮平联合使用则无此效果。这些结果表明，亚慢性0.2%碳酸锂治疗增强了全身性米氮平的抗焦虑样作用。这种增效疗法可能对焦虑症的治疗有用。
