Blockade of central β‐adrenoceptors attenuates tremor induced by 5‐hydroxytryptamine (5‐HT)‐receptor activation in rats

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Abstract
The effect of β‐adrenoceptor antagonists, varying in lipophilicity and receptor selectivity, were studied on tremor elicited byl‐5‐hydroxytryptophan (L‐5‐HTP) in rats pretreated with a peripherally acting decarboxylase inhibitor and a monoamine oxidase inhibitor, or by the directly acting 5‐HT agonist s‐methoxy‐N,N‐dimethyltryptamine (5‐MeODMT). Plasma levels of the β‐adrenoceptor antagonists were determined simultaneously. The non‐selective lipophilic adrenoceptor antagonist propranolol was found to dose‐dependently reduce tremor intensity, whereas the non‐selective hydrophilic adrenoceptor antagonist sotalol had no effect, indicating a central site of action. Furthermore, β1‐selective blockade with the adrenoceptor antagonist metoprolol had no effect on tremor intensity, whereas the β2‐selective antagonist ICI 118,551 dose‐dependently suppressed tremor intensity, suggesting that the β‐adrenoceptor subtype involved is of the β2‐type. These results suggest that blockade of centrally located β2‐adrenoceptors are able to attenuate the tremor response following 5‐hydroxytryptamine receptor activation.