Drug-induced changes of epinephrine turnover in the rat hypothalamus

The effects of various psychotropic agents on the steady state levels and on the FLA 63-induced disappearance of hypothalamic epinephrine have been investigated in the rat. Desipramine retarded the utilization without affecting the basal levels of epinephrine while mianserin accelerated epinephrine utilization and reduced the steady state concentrations of the transmitter. In contrast, chlorimipramine, iprindole and trazodone were without effect. An acceleration of epinephrine utilization and a reduction of basal epinephrine levels were also observed after administration of (α-adrenolytic doses of) neuroleptic agents (chlorpromazine, haloperidol, clozapine, thioridazine) or (+)-amphetamine and cocaǐne but sulpiride or the dopamine receptor agonists apomorphine and bromocriptine were without effect. The clonidine-induced retardation of epinephrine utilization was antagonized by yohimbine, phenoxybenzamine, mianserin, haloperidol and chlorpromazine but not by desipramine or trazodone. These data indicate that α-adrenoceptors are involved in the regulation of epinephrine release and mediate the action of psychotropic agents. The cholinomimetic agent oxotremorine increased epinephrine utilization; this effect was abolished by atropine. In contrast, diazepam or GABAmimetic agents failed to affect epinephrine utilization. These results suggest cholinergic but not GABAergic regulation of epinephrine turnover.