Selective blockade of brain? 2-autoreceptors by yohimbine: Effects on motor activity and on turnover of noradrenaline and dopamine

Abstract

Summary The motor activity of groups of three mice was increased by yohimbine at doses up to 3 mg/kg intraperitoneally. The turnover of dopamine and noradrenaline in the mouse brain, as assessed by the disappearance of catecholamines following treatment with the tyrosine hydroxylase inhibitorα-methyltyrosine, was accelerated by yohimbine with a peak effect after 10 mg/kg intraperitoneally. Prazosin (3 mg/kg i.p.) completely antagonized the stimulatory effect of yohimbine on motor activity and on dopamine turnover but it somewhat potentiated the stimulatory effect on the turnover of noradrenaline. Amphetamine reversed the prazosin-induced hypomotility, indicating that prazosin can selectively block postsynapticα ₁-receptors. Yohimbine did not stimulate motor activity following 10 mg/kg and it retarded the turnover of dopamine following 30 mg/kg. These actions might be due to blockade of postsynapticα-receptors by yohimbine. The data indicate that yohimbine at low doses stimulates motor activity and dopamine turnover by selectively blockingα ₂-autoreceptors leading to increased release of noradrenaline and subsequent activation of postsynapticα ₁-receptors.