Modulation of oxotremorine‐induced tremor by central β‐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 β-adrenoceptor antagonist propranolol dose-dependently suppressed tremor intensity, whereas the r-isomer of propranolol was without effect, verifying β-adrenoceptor involvement. Since the hydrophilic, non-selective β-antagonist nadolol was ineffective, the effect appears to be located inside the blood-brain barrier. The β2-selective antagonist ICI 118, 551 dose-dependently reduced tremor intensity, whereas selective blockade of β1-adrenoceptors with metoprolol had no effect, indicating the participation of a β2-adrenoceptor. On the other hand, the lipophilic β2-agonist clenbuterol dose-dependently enhanced tremor induced by oxotremorine. Determination of circulating plasma catecholamine concentrations revealed that the effect of β-antagonists on tremor was not secondary to an effect on the oxotremorine-induced rise in catecholamine levels. Thus, the results suggest that β2-adrenocpetors located inside the blood-brain barrier are able to modulate oxotremorine-induced tremor in rats.