PHENETHYLAMINE (PEA), THE DOPAMINE TRANSPORTER AND COCAINE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：单胺转运体调节神经递质水平，释放或隔离它们进入神经元。可卡因和其他精神兴奋剂抑制多巴胺（DAT）和去甲肾上腺素（NET）转运蛋白，其相对效力与其产生兴奋剂作用和滥用倾向的效力相关。微量胺苯乙胺（PEA）与成瘾有关，但PEA、单胺转运体和药物之间的关系尚不清楚。我们假设PEA是DAT和NET的底物，药物将有效地抑制[3 H]PEA转运，DAT抑制剂对（3 H）PEA转运的阻断与可卡因样药物的刺激和增强特性有关。方法：我们测量了（3 H）PEA转运动力学，比较了药物对人DAT-HEK-293细胞中（3 H）PEA和（3 H）多巴胺转运的影响，并将体外相对药物效力与已报道的在灵长类动物中产生行为效应的药物效力进行了比较。结果：（3 H）PEA转运活跃，DAT和NET亲和力与（3 H）多巴胺或（3 H）去甲肾上腺素亲和力相似。（-）-钴和其他药物剂量依赖性地抑制DAT的PEA转运，其效力大于阻断（3 H）多巴胺转运的药物。阻断（3 H）PEA转运的药物的相对效力与其在灵长类动物中产生精神刺激和维持自我给药的相对效力高度相关。结论：DAT和NET对PEA转运的药物抑制可使脑细胞外PEA水平升高。这些结果暗示PEA和微量胺受体1激活作为DAT抑制剂的精神兴奋剂和强化作用的贡献者。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. AIMS: Monoamine transporters regulate neurotransmitter levels, which release or sequester them from and into neurons. Cocaine and other psychostimulants inhibit the dopamine (DAT) and norepinephrine (NET) transporters, with relative potencies that correlate with their potencies for producing stimulant effects and abuse liability. The trace amine phenylethylamine (PEA) is implicated in addiction, but the relationship between PEA, monoamine transporters and drugs is unknown. We postulated that PEA is a substrate for the DAT and NET, that drugs would potently inhibit [3H]PEA transport and that blockade of (3H)PEA transport by DAT inhibitors would be relevant to the stimulant and reinforcing properties of cocaine-like drugs. METHODS: We measured (3H)PEA transport kinetics, compared drug effects on (3H)PEA and (3H)dopamine transport in human DAT-HEK-293 cells, and compared relative drug potencies in vitro with reported drug potencies for producing behavioral effects in primates. RESULTS: (3H)PEA was actively transported, with DAT and NET affinities similar to (3H)dopamine or (3H)norepinephrine affinities. (-)-Cocaine and other drugs dose-dependently inhibited PEA transport by the DAT, at greater potencies than those that block (3H)dopamine transport. The relative potencies of drugs for blocking (3H)PEA transport correlated highly with their reported relative potencies for producing psychomotor stimulation and maintaining self-administration in primates. CONCLUSIONS: Drug inhibition of PEA transport by the DAT and NET conceivably elevates extracellular PEA levels in brain. These results implicate PEA and the trace amine receptor1 activation as contributors to the psychostimulant and reinforcing effects of DAT inhibitors.