Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8553, Japan.
Behav Brain Res. 2011 Jan 1;216(1):46-52. doi: 10.1016/j.bbr.2010.07.002. Epub 2010 Jul 8.
Growing evidence indicates that the glutamatergic neurotransmitter system is central to the neurobiology and treatment of depression. Riluzole, a drug currently used to slow the progression of amyotrophic lateral sclerosis (ALS), directly affects the glutamatergic system. In this study, we investigated the effects of riluzole in olfactory bulbectomy (OBX) rats, an animal model of depression. The olfactory bulbs in rats were removed by suction. The emotionality of rats was measured by scoring their responses to given stimuli, i.e., attack, startle, struggle, and fight responses. The OBX rats chronically treated with vehicle for 7 days at 14 days following surgery showed significant increases in emotionality responses. Single (1st day administration) and subchronic (7th day administration) riluzole treatment (1-10 mg/kg, po) significantly and dose-dependently reduced hyperemotional responses in OBX rats. Both single and subchronic riluzole treatment (10 mg/kg, po) had no significant effects on the emotional responses in sham operated rats. In addition, we demonstrated that single riluzole treatment (10 mg/kg, po) significantly decreased extracellular glutamate levels in medial prefrontal cortex of OBX rats by in vivo microdialysis. We provide the first experimental evidence that riluzole rapidly attenuated hyperemotional responses in OBX rats, an animal model of depression.
越来越多的证据表明，谷氨酸能神经递质系统是抑郁症的神经生物学和治疗的核心。利鲁唑是一种目前用于减缓肌萎缩侧索硬化症（ALS）进展的药物，它直接影响谷氨酸能系统。在这项研究中，我们研究了利鲁唑对嗅球切除术（OBX）大鼠的影响，OBX 大鼠是一种抑郁症动物模型。通过抽吸去除大鼠的嗅球。通过评分大鼠对给定刺激的反应来测量大鼠的情绪反应，即攻击、惊吓、挣扎和战斗反应。手术后 14 天连续 7 天给予载体的 OBX 大鼠表现出情绪反应显著增加。单次（第 1 天给药）和亚慢性（第 7 天给药）利鲁唑治疗（1-10mg/kg，po）显著且剂量依赖性地降低 OBX 大鼠的过度情绪化反应。单次和亚慢性利鲁唑治疗（10mg/kg，po）对假手术大鼠的情绪反应均无显著影响。此外，我们证明单次利鲁唑治疗（10mg/kg，po）通过体内微透析显著降低了 OBX 大鼠内侧前额叶皮质的细胞外谷氨酸水平。我们提供了第一个实验证据，表明利鲁唑可迅速减轻抑郁症动物模型 OBX 大鼠的过度情绪化反应。
