Martin Fredricka C, Thu Le Anh, Handforth Adrian
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.
Mov Disord. 2005 Mar;20(3):298-305. doi: 10.1002/mds.20331.
No preclinical method to evaluate potential new medications for essential tremor (ET) is available currently. Although harmaline tremor is a well known animal model of ET, it has not found utility as a preclinical drug screen and has not been validated with anti-ET medications. We measured harmaline tremor in rats (10 mg/kg s.c.) and mice (20 mg/kg s.c.) with a load sensor under the cage floor and performed spectral analysis on 20-minute epochs. The motion power over the tremor frequency bandwidth (8-12 Hz in rats; 10-16 Hz in mice) was divided by the motion power over the full motion frequency range (0-15 Hz in rats; 0-34 Hz in mice). The use of these measures greatly reduced data variability, permitting experiments with small sample sizes. Three drugs that suppress ET (propranolol, ethanol, and octanol) all significantly suppressed harmaline-induced tremor. We propose that, with this methodology, harmaline-induced tremor may be useful as a preclinical method to identify potential medications for ET.
目前尚无评估特发性震颤（ET）潜在新药的临床前方法。虽然哈马灵震颤是一种广为人知的ET动物模型，但它尚未被用作临床前药物筛选，也未用抗ET药物进行验证。我们用置于笼底的负载传感器测量大鼠（皮下注射10mg/kg）和小鼠（皮下注射20mg/kg）的哈马灵震颤，并对20分钟时段进行频谱分析。将震颤频率带宽（大鼠为8 - 12Hz；小鼠为10 - 16Hz）内的运动功率除以全运动频率范围（大鼠为0 - 15Hz；小鼠为0 - 34Hz）内的运动功率。使用这些测量方法大大降低了数据变异性，使得能够进行小样本量的实验。三种抑制ET的药物（普萘洛尔、乙醇和辛醇）均显著抑制了哈马灵诱导的震颤。我们提出，采用这种方法，哈马灵诱导的震颤可能作为一种临床前方法用于识别ET的潜在药物。
