ANTIDOPAMINERGIC PROPERTIES OF YOHIMBINE

Abstract

The effect of .alpha. adrenoceptor blocking agent yohimbine on cerebral dopamine metabolism was investigated in the rat. Yohimbine (1-10 mg/kg i.p.) increased in both striatum and limbic areas homovanillic acid and dihydroxyphenylacetic acid levels, tyrosine hydroxylase activity measured in vitro, the in vivo accumulation of dihydroxyphenylalanine after NSD 1015 [3-hydroxybenzylhydrazine fumarate] and the rate of dopamine disappearance after .alpha.-methyl-p-tyrosine. The inability of clonidine to prevent the yohimbine-induced enhancement of striatal homovanillic acid levels in doses that antagonize the yohimbine-induced increase in noradrenaline [norepinephrine] turnover and the failure of other .alpha. adrenoceptor blocking agents (tolazoline, phentolamine and prazosin) to increase dopamine metabolism suggest that .alpha. adrenoceptors are not involved in the yohimbine-induced alteration of dopamine metabolism. Similarly to neuroleptic agents, yohimbine reduced striatal acetylcholine concentrations and counteracted the dopamine (10-5 M)-induced inhibition of the K evoked release of [3H]acetylcholine from slices of caudate nucleus. Yohimbine failed to enhance striatal homovanillic acid levels in animals pretreated with a supramaximal dose of haloperidol. In rats treated with haloperidol for 10 days, the effect of yohimbine on striatal homovanillic acid and acetylcholine levels was markedly reduced. Yohimbine possesses postsynaptic dopamine receptors blocking properties in addition to its ability to inhibit .alpha. adrenergic receptors. The failure of yohimbine to affect dopamine-sensitive adenylate cyclase activity in striatal homogenates suggests an action of the compound on the D2 receptor.