Modulation of oxotremorine-induced tremor by central beta-adrenoceptors

The muscarinic agonist oxotremorine was used to induce tremor in rats pretreated with methylatropine. An objective assessment of tremor intensity was accomplished by means of an accelerometer-based recording system. The non-selective, lipophilic beta-adrenoceptor antagonist propranolol dose-dependently suppressed tremor intensity, whereas the R-isomer of propranolol was without effect, verifying beta-adrenoceptor involvement. Since the hydrophilic, non-selective beta-antagonist nadolol was ineffective, the effect appears to be located inside the blood-brain barrier. The beta 2-selective antagonist ICI 118, 551 dose-dependently reduced tremor intensity, whereas selective blockade of beta 1-adrenoceptors with metoprolol had no effect, indicating the participation of a beta 2-adrenoceptor. On the other hand, the lipophilic beta 2-agonist clenbuterol dose-dependently enhanced tremor induced by oxotremorine. Determination of circulating plasma catecholamine concentrations revealed that the effect of beta-antagonists on tremor was not secondary to an effect on the oxotremorine-induced rise in catecholamine levels. Thus, the results suggest that beta 2-adrenoceptors located inside the blood-brain barrier are able to modulate oxotremorine-induced tremor in rats.