Tremor induction by intracaudate injections of bretylium, tetrabenazine, or mescaline: Functional deficits in caudate dopamine

Abstract

Tremor responses were evoked by intracaudate injections of tetrabenazine, bretylium, or mescaline in cats with chronically implanted recording electrodes and microinjection cannulas. The characteristics of the maximal tremors with each agent closely resembled those induced by increased levels of cholinergic activity in the caudate (previously reported). These maximal tremors, like the cholinergic tremors, were suppressed by local injections of catecholamines (dopamine and epinephrine), scopolamine, or hemicholinium but were intensified by intracaudate serotonin. Although local acetylcholine had no effect on established tremor activity, tremors abolished by hemicholinium were reestablished by small doses of acetylcholine. These results suggested that interference with local dopamine inhibitory mechanisms (“functional dopamine deficiency”) was the basis for the tremorgenic actions of bretylium, tetrabenazine, and mescaline; the findings also indicated that sustained endogenous acetylcholine activity in the caudate was a necessary condition for the development and maintenance of tremor activity. These data lend support to the hypothesis that an imbalance in the caudate between dopamine inhibition and acetylcholine excitation in favor of the latter results in tremors. Copyright © 1973 Wiley‐Liss, Inc., A Wiley Company