Harmaline-Induced Essential Tremor
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Harmaline has been demonstrated to produce a 10-16 Hz tremor in mice, rats, and guinea pigs and is a standard preclinical model of essential tremor (Martin et al, 1986; Handforth, 2012). Tremor can be assessed via a force plate actimeter and can be blocked or attenuated by propranolol, ethanol, and other alcohols.
In the figure below, propranolol or saline (Drug 1) were administered following a baseline recording period, and 15 minutes later, saline or harmaline (15 mg/kg IP; Drug 2) was administered in a crossover design. Saline or propranolol alone had no effect on tremor, while harmaline alone significantly increased tremor from 10 – 20 minutes after administration. In contrast, propranolol pre-treatment completely blocked the tremorigenic effect of harmaline. Similar results were obtained with 10% or 14% ethanol.
The Harmaline Essential Tremor model is an acute procedure that can be conducted in one day and is normally used to evaluate test articles after a single administration. Groups sizes of 8-12 animals are typically used.
Handforth, A. Harmaline Tremor: Underlying Mechanisms in a Potential Animal Model of Essential Tremor. Tremor and Other Hyperkinetic Movements, pps. 1-14. http://www.tremorjournal.org.
Martin FC, Thu Le A, Handforth A. Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications. Mov Disord. 2005; 20(3):298-305.