Selective blockade of brain alpha 2-autoreceptors by yohimbine: effects on motor activity and on turnover of noradrenaline and dopamine.
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 inhibitor alpha-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 postsynaptic alpha 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 postsynaptic alpha-receptors by yohimbine. The data indicate that yohimbine at low doses stimulates motor activity and dopamine turnover by selectively blocking alpha 2-autoreceptors leading to increased release of noradrenaline and subsequent activation of post-synaptic alpha 1-receptors.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology*; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D019805:alpha-Methyltyrosine; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine; D011224:Prazosin