Pramipexole at a Low Dose Induces Beneficial Effect in the Harmaline-induced Model of Essential Tremor in Rats

The aim of the study was to examine the effects of preferential agonists of dopamine D3 receptors: pramipexole and 7-OH-DPAT on the harmaline-induced tremor in rats (a model of essential tremor, ET). To study receptor mechanisms of these drugs, rats were pretreated with dopamine D3 receptor antagonists--SB-277011-A and SR-21502, an antagonist of presynaptic D2/D3 receptors--amisulpride, or a nonselective antagonist of D2-like receptors, haloperidol, at a postsynaptic dose.

For tremor measurement, fully automated force plate actimeters were used and data were analyzed using fast Fourier transform.

Harmaline (15 mg/kg ip)-triggered tremor was manifested by an increase in the power within 9-15 Hz band (AP2). Pramipexole administered at a low (0.1 mg/kg sc), but not higher doses (0.3 and 1 mg/kg sc), and 7-OH-DPAT (0.1, 0.3, and 1 mg/kg sc) reversed the harmaline-increased AP2. None of the examined dopamine antagonists: SB-277011-A (10 mg/kg ip), SR-21502 (15 mg/kg ip), haloperidol (0.5 mg/kg ip), or amisulpride (1 mg/kg ip) influenced the above effect of dopamine agonists.

The present study indicates that pramipexole reduces the harmaline-induced tremor, which may suggest its beneficial effects in ET patients. However, mechanisms underlying its action are still unclear and need further examination.