New York University Langone School of Medicine, Department of Psychiatry, 550 First Ave, New York, NY, USA.
Int J Neuropsychopharmacol. 2011 Jun;14(5):691-6. doi: 10.1017/S1461145710001161. Epub 2010 Sep 29.
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.
这项研究旨在复制先前的一项发现，即在慢性抑郁的啮齿动物中，脑内给予抗抑郁药可迅速产生急性治疗作用。将急性第四脑室（ivt.）注射的效果与急性外周（i.p.）给予去甲丙咪嗪（DMI）的效果进行了比较，这些啮齿动物接受了重复的开放式强迫游泳。经证实，单次 ivt. 注射低（3 nmol）但不高（30 nmol）剂量即可立即逆转模型的不动性和不活动性，而急性 i.p. 给药在高达 30 mg/kg 时均无效。单次 i.p. 注射中等剂量（10 mg/kg）后，还发现重复的强迫游泳应激可显著减少 DMI 在脑内的净积累，但对肝脏无影响。结果表明，应激诱导的中枢神经系统内区域性药物摄取或代谢改变可能有助于解释在高痛苦障碍中抗抑郁药和其他化合物的治疗滞后。
