Robertson S D, Matthies H J G, Galli A
Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, USA.
Mol Neurobiol. 2009 Apr;39(2):73-80. doi: 10.1007/s12035-009-8053-4. Epub 2009 Feb 6.
Amphetamine (AMPH) and its derivatives are regularly used in the treatment of a wide array of disorders such as attention-deficit hyperactivity disorder (ADHD), obesity, traumatic brain injury, and narcolepsy (Prog Neurobiol 75:406-433, 2005; J Am Med Assoc 105:2051-2054, 1935; J Am Acad Child Adolesc Psychiatry 41:514-521, 2002; Neuron 43:261-269, 2004; Annu Rev Pharmacol Toxicol 47:681-698, 2007; Drugs Aging 21:67-79, 2004). Despite the important medicinal role for AMPH, it is more widely known for its psychostimulant and addictive properties as a drug of abuse. The primary molecular targets of AMPH are both the vesicular monoamine transporters (VMATs) and plasma membrane monoamine-dopamine (DA), norepinephrine (NE), and serotonin (5-HT)-transporters. The rewarding and addicting properties of AMPH rely on its ability to act as a substrate for these transporters and ultimately increase extracellular levels of monoamines. AMPH achieves this elevation in extracellular levels of neurotransmitter by inducing synaptic vesicle depletion, which increases intracellular monoamine levels, and also by promoting reverse transport (efflux) through plasma membrane monoamine transporters (J Biol Chem 237:2311-2317, 1962; Med Exp Int J Exp Med 6:47-53, 1962; Neuron 19:1271-1283, 1997; J Physiol 144:314-336, 1958; J Neurosci 18:1979-1986, 1998; Science 237:1219-1223, 1987; J Neurosc 15:4102-4108, 1995). This review will focus on two important aspects of AMPH-induced regulation of the plasma membrane monoamine transporters-transporter mediated monoamine efflux and transporter trafficking.
苯丙胺（AMPH）及其衍生物常用于治疗多种疾病，如注意力缺陷多动障碍（ADHD）、肥胖症、创伤性脑损伤和发作性睡病（《神经生物学进展》75:406 - 433，2005；《美国医学会杂志》105:2051 - 2054，1935；《美国儿童与青少年精神病学学会杂志》41:514 - 521，2002；《神经元》43:261 - 269，2004；《药物毒理学年度评论》47:681 - 698，2007；《药物与衰老》21:67 - 79，2004）。尽管AMPH具有重要的药用价值，但其作为一种滥用药物的精神刺激和成瘾特性更为人所知。AMPH的主要分子靶点是囊泡单胺转运体（VMATs）和质膜单胺 - 多巴胺（DA）、去甲肾上腺素（NE）和5 - 羟色胺（5 - HT）转运体。AMPH的奖赏和成瘾特性依赖于其作为这些转运体底物的能力，并最终增加细胞外单胺水平。AMPH通过诱导突触囊泡耗竭来实现神经递质细胞外水平的升高，这会增加细胞内单胺水平，还通过促进质膜单胺转运体的逆向转运（外流）来实现（《生物化学杂志》237:2311 - 2317，1962；《医学实验（国际实验医学杂志）》6:47 - 53，1962；《神经元》19:1271 - 1283，1997；《生理学杂志》144:314 - 336，1958；《神经科学杂志》18:1979 - 1986，1998；《科学》237:1219 - 1223，1987；《神经科学杂志》）。本综述将聚焦于AMPH诱导的质膜单胺转运体调节中的两个重要方面——转运体介导的单胺外流和转运体 trafficking。（注：原文中“trafficking”未翻译完整，可能是拼写有误，正常应翻译为“运输、 trafficking”等，这里保留原文） 15:4102 - 4108，1995）。
