LAUSR

The primary cause of harmaline tremor, which is a model of essential tremor (ET) in animals, is excessive activation of olivocerebellar glutamatergic climbing fibers. Our recent study indicated that 5'-chloro-5'-deoxy-(±)-ENBA (5'Cl5'd-(±)-ENBA), a potent and selective adenosine A1 receptor agonist, inhibited harmaline tremor. The present study was aimed to evaluate the role of glutamatergic transmission system in 5'Cl5'd-(±)-ENBA tremorolytic action in the harmaline model in rats, by analyzing glutamate release in the motor nuclei of the thalamus and mRNA expression of glutamatergic neuron markers (vGlut1/2) in reference to the general neuronal activity marker (zif-268) in different brain structures. The extracellular glutamate level in the motor thalamus was evaluated by in vivo microdialysis and the vGlut1/vGlut2 and zif-268 mRNA expression was analyzed by in situ hybridization. The intensity of tremor was measured automatically using Force Plate Actimeters. 5'Cl5'd-(±)-ENBA (0.5mg/kg) given 30 min before harmaline (30mg/kg) decreased the harmaline-induced excessive glutamate release in the motor thalamus and reversed harmaline-induced molecular effects, such as elevation of the vGlut1 mRNA expression in the inferior olive and decrease in the motor cortex, as well as an increase of the zif-268 mRNA expression in the inferior olive, motor thalamus and motor cortex. Moreover, 5'Cl5'd-(±)-ENBA reduced harmaline tremor by lowering its power in 9-15 Hz frequency band. Our findings show that adenosine A1 receptor stimulation decreases glutamate release in the motor thalamic nuclei in a harmaline model of ET, suggesting that A1 receptors, especially in this structure, may be a potential therapeutic target in this disorder.