Harmalineā€induced tremor as a potential preclinical screening method for essential tremor medications

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Abstract
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 antiā€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 20ā€minute epochs. The motion power over the tremor frequency bandwidth (8ā€“12 Hz in rats; 10ā€“16 Hz in mice) was divided by the motion power over the full motion frequency range (0ā€“15 Hz in rats; 0ā€“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 harmalineā€induced tremor. We propose that, with this methodology, harmalineā€induced tremor may be useful as a preclinical method to identify potential medications for ET. Ā© 2004 Movement Disorder Society