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 gene zif-268 mRNA expression. Tremor in rats was induced by harmaline administered at a dose of 15 mg/kg ip. Pramipexole was administered at a low dose of 0.1 mg/kg sc. 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. The zif-268 mRNA expression was analyzed by in situ hybridization in brain slices. Harmaline induced tremor and increased zif-268 mRNA levels in the inferior olive, cerebellar cortex, ventroanterior/ventrolateral thalamic nuclei and motor cortex. Pramipexole reversed both the harmaline-induced tremor and the increase in zif-268 mRNA expression in the inferior olive, cerebellar cortex and motor cortex. Moreover, the tremor intensity correlated positively with zif-268 mRNA 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.

原发性震颤是最常见的神经系统疾病之一，但是，目前可用的药物治疗并不能充分控制它。我们最近的研究表明，普拉克索（一种可有效抑制帕金森病性震颤的药物）可减轻一般认为是原发性震颤模型的大鼠中由harmaline引起的震颤。本研究的目的是通过确定早期活动依赖性基因zif-268 mRNA的表达来研究普拉克索的溶血作用的脑靶标。以15 mg / kg腹膜内注射harmaline诱发大鼠震颤。普拉克索以0.1 mg / kg sc的低剂量给药。震颤用测力板测力计测量，其中位于测角板角下方的四个测力传感器跟踪动物在笛卡尔平面上的位置。在ZIF-268 mRNA的表达，在大脑切片原位杂交分析。在下橄榄，小脑皮层，腹前/腹侧丘脑核和运动皮层中，Harmaline引起震颤并增加zif -268 mRNA水平。普拉克索逆转了下橄榄，小脑皮层和运动皮层中由harmaline引起的震颤和zif-268 mRNA表达的增加。此外，震颤强度与zif-268正相关上述结构中的mRNA表达。目前的结果似乎表明普拉克索的溶血作用与震颤网络（包括下橄榄，小脑皮层和运动皮层）中伤害增加的神经元活性的调节有关。讨论了上述普拉克索作用的潜在机制。