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

Mov Disord. 2005 Mar;20(3):298-305. doi: 10.1002/mds.20331.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System Depressants / pharmacology
  • Central Nervous System Depressants / therapeutic use*
  • Central Nervous System Stimulants / adverse effects*
  • Essential Tremor* / chemically induced
  • Essential Tremor* / diagnosis
  • Essential Tremor* / drug therapy
  • Ethanol / pharmacology
  • Ethanol / therapeutic use*
  • Female
  • Harmaline / adverse effects*
  • Locomotion / drug effects
  • Mice
  • Mice, Inbred ICR
  • Propranolol / pharmacology
  • Propranolol / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use*

Substances

  • Central Nervous System Depressants
  • Central Nervous System Stimulants
  • Vasodilator Agents
  • Ethanol
  • Propranolol
  • Harmaline