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

Abstract

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.

Tremorolytic effect of 5′‐chloro‐5′‐deoxy‐(±)‐ENBA, a potent and selective adenosine A1 receptor agonist, evaluated in the harmaline‐induced model in rats

“…As reported previously, harmaline induced generalized tremor of the whole body which started as early as a few minutes after its administration and was manifested by an increase in power within the frequency band of 9‐15 HZ (AP2), and in the tremor index (Figures , and 4). Moreover, a decrease in the power within the frequency band of 0‐8 Hz (AP1) was noted within the first 30 minutes of measurement (Figures , and 4).…”

“…As reported previously, [6][7][8] Harmaline altered additionally locomotor activity of rats, measured by the total distance traveled. In agreement with our previous study, 7,8 this drug reduced exploratory activity during the first 30 minutes after its injection but later (30-60 minutes) it increased motility of rats (Figures 2 and 4).…”

“…Harmaline hydrochloride dihydrate (Sigma‐Aldrich, St Louis, MO, USA) was dissolved in redistilled water and administered as previously described at a dose of 15 mg/kg ip, immediately before tremor measurements, which lasted 60 minutes. 5′‐Chloro‐5′‐deoxy‐N 6 ‐(±)‐( endo ‐norborn‐2‐yl)adenosine (5′Cl5′d‐(±)‐ENBA, Tocris Cookson Ltd., Bristol, UK) was dissolved in 0.5% DMSO in physiological saline and administered at doses of 0.01‐0.5 mg/kg ip 30 minutes before harmaline.…”

“…Besides phenomenological similarities between ET and the harmaline‐induced tremor, their pharmacological treatments are also analogical . Moreover, a recent study has shown that, similar to its beneficial effect in ET, high‐frequency stimulation of the ventrolateral thalamic nucleus in mice (a region receiving glutamatergic projections from deep cerebellar nuclei) reduced the harmaline‐induced tremor .…”

“…2 Similar to ET, 3 the harmalineinduced tremor is postural and kinetic, and its peak frequency in rats is 10-12 Hz. 2,[4][5][6][7][8][9] It has been suggested that the harmaline-induced tremor is related to rhythmic firing of inferior olive neurons, 2,10 activation of the olivo-cerebellar glutamatergic climbing fibers, 2 elevation of glutamate release in the cerebellum, 11,12 and an increase in complex spike discharges of Purkinje cells (PCs) of the cerebellar cortex. 10 Moreover, harmaline induces oscillations in deep cerebellar nuclei, medullary reticular formation, and spinal cord 10,13,14 and activates c-Fos expression in the olivo-cerebellar system and in the basal ganglia.…”