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

Abstract

Aim: The aim of this study was to examine the role of adenosine A1 receptors in the harmaline-induced tremor in rats using 5′-chloro-5′-deoxy-(±)-ENBA (5′Cl5′d-(±)-ENBA), a brain-penetrant, potent, and selective adenosine A1 receptor agonist. Methods: Harmaline was injected at a dose of 15 mg/kg ip and tremor was measured automatically in force-plate actimeters by an increased averaged power in the frequency band of 9-15 Hz (AP2) and by tremor index (a difference in power between AP2 and averaged power in the frequency band of 0-8 Hz). The zif-268 mRNA expression was additionally analyzed by in situ hybridization in several brain structures. Results: 5′Cl5′d-(±)-ENBA (0.05-0.5 mg/kg ip) dose dependently reduced the harmaline-induced tremor and this effect was reversed by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective antagonist of adenosine A1 receptors (1 mg/kg ip). Harmaline increased the zif-268 mRNA expression in the inferior olive, cerebellar cortex, ventroanterior/ventrolateral thalamic nuclei, and motor cortex. 5′Cl5′d-(±)-ENBA reversed these increases in all the above structures. DPCPX reduced the effect of 5′Cl5′d-(±)-ENBA on zif-268 mRNA in the motor cortex. Conclusion: This study suggests that adenosine A1 receptors may be a potential target for the treatment of essential tremor.