Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications.
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.
Martin
Fredricka C
FC
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA. fredricka.martin@med.va.gov
Thu Le
Anh
A
Handforth
Adrian
A
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D020329:Essential Tremor / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D000431:Ethanol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006246:Harmaline / Q000009:adverse effects*; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D014665:Vasodilator Agents; D000431:Ethanol; D011433:Propranolol; D006246:Harmaline