Harmaline-Induced Essential Tremor

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Essential Tremor
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.

Propanol blocks harmaline-induced essential tremor.

Tremor (10-16 Hz) before (baseline; Bsln) and after treatment with saline or propranolol (Drug 1) followed by saline or harmaline (Drug 2). Saline or propranolol alone had no effect on body tremor. Harmaline alone significantly increased body tremor, while propranolol completely blocked the effect of harmaline. Values are mean ± SEM. **** p < 0.001, 2-way ANOVA, (N=7-12).

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.

References

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.