Geracitano Raffaella, Federici Mauro, Prisco Simonetta, Bernardi Giorgio, Mercuri Nicola B
Department of Experimental Neurology, Fondazione Santa Lucia-IRCCS, Via Ardeatina 306, 00179 Rome, Italy.
Neuropharmacology. 2004 May;46(6):807-14. doi: 10.1016/j.neuropharm.2003.11.031.
Trace amines are biological compounds that are still awaiting identification of their role in neuronal function. Using intracellular electrophysiological recordings, we investigated the depressant action of two trace amines (beta-phenylethylamine and tyramine) on the firing activity of dopaminergic neurons of the substantia nigra pars compacta and ventral tegmental area. This inhibition was due to a membrane hyperpolarisation that was blocked by the D2 dopamine receptor antagonist sulpiride and was not potentiated by the dopamine-uptake blocker, cocaine. Inhibition of the dopamine transporter did not mediate the effects of trace amines, because unlike cocaine, trace amines did not potentiate the inhibitory responses to exogenously applied dopamine. The inhibitory actions of beta-phenylethylamine and tyramine were present in reserpine-treated animals but were abolished when the dopamine-synthesis inhibitor carbidopa was applied. Our data suggest that trace amines cause an indirect activation of dopamine autoreceptors, by an increased efflux of newly synthesised dopamine. The inhibition of dopaminergic activity by trace amines may relate to their involvement in neuronal processes linked to drug addiction, schizophrenia, attention deficit hyperactive disorders and Parkinson's disease.
痕量胺是一类生物化合物，其在神经元功能中的作用仍有待确定。我们利用细胞内电生理记录，研究了两种痕量胺（β-苯乙胺和酪胺）对黑质致密部和腹侧被盖区多巴胺能神经元放电活动的抑制作用。这种抑制作用是由于膜超极化所致，该超极化被D2多巴胺受体拮抗剂舒必利阻断，且未被多巴胺摄取阻滞剂可卡因增强。多巴胺转运体的抑制并未介导痕量胺的作用，因为与可卡因不同，痕量胺并未增强对外源性多巴胺的抑制反应。β-苯乙胺和酪胺的抑制作用在利血平处理的动物中存在，但在应用多巴胺合成抑制剂卡比多巴后消失。我们的数据表明，痕量胺通过增加新合成多巴胺的外流，间接激活多巴胺自身受体。痕量胺对多巴胺能活性的抑制可能与其参与与药物成瘾、精神分裂症、注意力缺陷多动障碍和帕金森病相关的神经元过程有关。
