Harmaline‐induced tremor as a potential preclinical screening method for essential tremor medications

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 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. © 2004 Movement Disorder Society