Pramipexole Reduceszif-268mRNA Expression in Brain Structures involved in the Generation of Harmaline-Induced Tremor

Essential tremor is one of the most common neurological disorders, however, it is not sufficiently controlled with currently available pharmacotherapy. Our recent study has shown that pramipexole, a drug efficient in inhibiting parkinsonian tremor, reduced the harmaline-induced tremor in rats, generally accepted to be a model of essential tremor. The aim of the present study was to investigate brain targets for the tremorolytic effect of pramipexole by determination of the early activity-dependent genezif-268mRNA expression. Tremor in rats was induced by harmaline administered at a dose of 15 mg/kgip. Pramipexole was administered at a low dose of 0.1 mg/kgsc. Tremor was measured by Force Plate Actimeters where four force transducers located below the corners of the plate tracked the animal's position on a Cartesian plane. Thezif-268mRNA expression was analyzed by in situ hybridization in brain slices. Harmaline induced tremor and increasedzif-268mRNA levels in the inferior olive, cerebellar cortex, ventroanterior/ventrolateral thalamic nuclei and motor cortex. Pramipexole reversed both the harmaline-induced tremor and the increase inzif-268mRNA expression in the inferior olive, cerebellar cortex and motor cortex. Moreover, the tremor intensity correlated positively withzif-268mRNA expression in the above structures. The present results seem to suggest that the tremorolytic effect of pramipexole is related to the modulation of the harmaline-increased neuronal activity in the tremor network which includes the inferior olive, cerebellar cortex and motor cortex. Potential mechanisms underlying the above pramipexole action are discussed.