Further evidence for an immediate antidepressant action of intracerebral drug administration in a model of chronic depression.
Further evidence for an immediate antidepressant action of intracerebral drug administration in a model of chronic depression.
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在慢性抑郁症模型中脑内给药具有立即抗抑郁作用的进一步证据。
DOI：
10.1017/s1461145710001161
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Stone,EricA
中科院分区：
文献类型：
--
作者：
Lin,Yan;Suckow,RaymondF;Sarfraz,Yasmeen;Stone,EricA
这项研究的目的是复制早期的发现，即脑内注射抗抑郁药对慢性抑郁的啮齿类动物具有快速急性治疗作用。将急性第四心室 (ivt.) 注射的效果与急性外周 (i.p.) 注射地昔帕明 (DMI) 的效果进行比较，小鼠反复进行开放空间强迫游泳。经确认，发现单个ivt。注射低剂量（3 nmol）但不是高剂量（30 nmol）立即逆转了模型的不动和不活动，而急性腹膜内注射则相反。给药剂量高达 30 mg/kg 时没有效果。研究还发现，单次腹腔注射后，反复强迫游泳压力可显着减少大脑中 DMI 的净积累，但不会减少肝脏中的 DMI 净积累。注射中等剂量（10mg/kg）。结果表明，压力引起的中枢神经系统区域药物摄取或代谢的改变可能导致抗抑郁药和其他化合物在高度痛苦的疾病中的治疗滞后。
This study was designed to replicate an earlier finding of a rapid acute therapeutic action of intracerebrally administered antidepressant in chronically depressed rodents. The effects of acute fourth ventricular (ivt.) injections were compared to those of acute peripheral (i.p.) injections of desipramine (DMI) in mice subjected to repeated open-space forced swim. In confirmation, it was found that a single ivt. injection of a low (3 nmol) but not high (30 nmol) dose immediately reversed the immobility and inactivity of the model whereas acute i.p. administration was without effect up to 30 mg/kg. The repeated forced swim stress was also found to significantly reduce the net accumulation of DMI in the brain but not liver after a single i.p. injection of a moderate dose (10 mg/kg). The results suggest that stress-induced alterations of regional drug uptake or metabolism in the CNS may contribute to the therapeutic lag for antidepressants and other compounds in disorders with high distress.