Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT 06508, USA.
Int J Neuropsychopharmacol. 2009 Nov;12(10):1421-8. doi: 10.1017/S1461145709990629. Epub 2009 Sep 24.
Clinical research has shown that co-administration of eszopiclone, a sedative-hypnotic sleeping agent, and fluoxetine, a serotonin uptake inhibitor, exerts an additive antidepressant action in treating patients with both depression and insomnia. Preclinical studies demonstrate that the behavioural actions of antidepressants are linked to neurogenesis in the adult hippocampus. To test the hypothesis that the additive effects of eszopiclone and fluoxetine could act via such a mechanism, the influence of combined administration of these agents on the proliferation and survival of bromodeoxyuridine (BrdU)-labelled newborn cells in the hippocampus of adult rats was determined. Chronic eszopiclone+fluoxetine co-administration significantly increased the survival, but not proliferation, of newborn neurons in dorsal hippocampus by approximately 50%, an effect greater than either drug alone. These findings are consistent with the hypothesis that eszopiclone enhances the antidepressant action of fluoxetine, in part via a novel mechanism that increases the survival of newborn neurons.
临床研究表明,镇静催眠药佐匹克隆与 5-羟色胺再摄取抑制剂氟西汀联合应用,对治疗同时患有抑郁症和失眠症的患者具有相加的抗抑郁作用。临床前研究表明,抗抑郁药的行为作用与成年海马体中的神经发生有关。为了验证佐匹克隆和氟西汀的相加作用可能通过这种机制发挥作用的假说,检测了联合应用这些药物对成年大鼠海马体中溴脱氧尿苷(BrdU)标记的新生细胞增殖和存活的影响。结果表明,佐匹克隆+氟西汀慢性联合给药可显著增加背侧海马体新生神经元的存活(约 50%),但不增加其增殖,其作用大于单独应用任何一种药物。这些发现与佐匹克隆增强氟西汀的抗抑郁作用的假说一致,部分原因是通过一种增加新生神经元存活的新机制。