Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan ; Medical Affairs, Dainippon Sumitomo Pharma, Co, Ltd, Tokyo, Japan.
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan.
Neuropsychiatr Dis Treat. 2014 Feb 11;10:289-95. doi: 10.2147/NDT.S55507. eCollection 2014.
Mirtazapine, a noradrenergic and specific serotonergic antidepressant, which blocks the α2-adrenergic autoreceptors and heteroreceptors, has shown anxiolytic properties in clinical trials and preclinical animal experiments. The addition of mirtazapine to selective serotonin reuptake inhibitors (SSRIs) is clinically suggested to be more effective for anxiety disorders. In this study, we examined the combined effects of mirtazapine and citalopram, an SSRI, on the freezing behavior of rats, which was induced by contextual conditioned fear as an index of anxiety or fear.
Male Sprague Dawley rats individually received footshocks in a shock chamber, and 24 hours later, they were given citalopram and/or mirtazapine injections. One hour after citalopram and 30 minutes after mirtazapine administration, freezing behavior was analyzed in the same shock chamber without shocks.
Mirtazapine decreased freezing in a dose-dependent manner, which is consistent with a previous report; it also enhanced an anxiolytic-like effect at a high dose (30 mg/kg) of citalopram. Because mirtazapine blocks α2-adrenoreceptors, the combined effect of atipamezole, a selective α2 receptor antagonist, with citalopram was also examined. Similar to mirtazapine, atipamezole reduced freezing dose-dependently, but the enhancement of citalopram's effects by atipamezole was not clear when compared with mirtazapine.
The present findings suggest that mirtazapine has an anxiolytic-like effect and may enhance the anxiolytic-like effect of SSRIs, but this enhancement may not be explained by its anti-α2 property alone.
米氮平是一种去甲肾上腺素能和特异性 5-羟色胺能抗抑郁药，可阻断 α2-肾上腺素能自受体和异受体，在临床试验和临床前动物实验中显示出抗焦虑特性。在临床上，米氮平联合选择性 5-羟色胺再摄取抑制剂（SSRIs）被建议对焦虑症更为有效。在这项研究中，我们检测了米氮平和西酞普兰（一种 SSRI）联合使用对大鼠的冻结行为的影响，该行为是通过上下文条件性恐惧作为焦虑或恐惧的指标诱导的。
雄性 Sprague Dawley 大鼠在一个电击室中接受单独的电击，24 小时后，给予西酞普兰和/或米氮平注射。在给予西酞普兰 1 小时后和米氮平 30 分钟后，在没有电击的情况下在同一电击室中分析冻结行为。
米氮平以剂量依赖性方式降低冻结，这与之前的报告一致；它还增强了西酞普兰高剂量（30mg/kg）的抗焦虑样作用。由于米氮平阻断 α2-肾上腺素受体，还检查了选择性 α2 受体拮抗剂阿替美唑与西酞普兰联合使用的效果。与米氮平类似，阿替美唑以剂量依赖性方式降低冻结，但与米氮平相比，阿替美唑增强西酞普兰的效果不明显。
本研究结果表明，米氮平具有抗焦虑样作用，可能增强 SSRIs 的抗焦虑样作用，但这种增强作用可能不仅仅通过其抗 α2 特性来解释。
