Howell Leonard L, Kimmel Heather L
Division of Neuroscience, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
Biochem Pharmacol. 2008 Jan 1;75(1):196-217. doi: 10.1016/j.bcp.2007.08.003. Epub 2007 Aug 7.
Psychostimulants are a broadly defined class of drugs that stimulate the central and peripheral nervous systems as their primary pharmacological effect. The abuse liability of psychostimulants is well established and represents a significant public health concern. An extensive literature documents the critical importance of monoamines (dopamine, serotonin and norepinephrine) in the behavioral pharmacology and addictive properties of psychostimulants. In particular, the dopamine transporter plays a primary role in the reinforcing and behavioral-stimulant effects of psychostimulants in animals and humans. Moreover, both serotonin and norepinephrine systems can reliably modulate the neurochemical and behavioral effects of psychostimulants. However, there is a growing body of evidence that highlights complex interactions among additional neurotransmitter systems. Cortical glutamatergic systems provide important regulation of dopamine function, and inhibitory amino acid gamma-aminobutyric acid (GABA) systems can modulate basal dopamine and glutamate release. Repeated exposure to psychostimulants can lead to robust and enduring changes in neurobiological substrates, including monoamines, and corresponding changes in sensitivity to acute drug effects on neurochemistry and behavior. Significant advances in the understanding of neurobiological mechanisms underlying psychostimulant abuse and dependence have guided pharmacological treatment strategies to improve clinical outcome. In particular, functional agonist treatments may be used effectively to stabilize monoamine neurochemistry, influence behavior and lead to long-term abstinence. However, additional clinical studies are required in order to identify safe and efficacious pharmacotherapies.
精神兴奋药是一类广义上定义的药物，其主要药理作用是刺激中枢和外周神经系统。精神兴奋药的滥用可能性已得到充分证实，是一个重大的公共卫生问题。大量文献证明了单胺类物质（多巴胺、5-羟色胺和去甲肾上腺素）在精神兴奋药的行为药理学和成瘾特性中的关键重要性。特别是，多巴胺转运体在精神兴奋药对动物和人类的强化及行为刺激作用中起主要作用。此外，5-羟色胺和去甲肾上腺素系统都能可靠地调节精神兴奋药的神经化学和行为效应。然而，越来越多的证据突出了其他神经递质系统之间复杂的相互作用。皮质谷氨酸能系统对多巴胺功能提供重要调节，抑制性氨基酸γ-氨基丁酸（GABA）系统可调节基础多巴胺和谷氨酸释放。反复接触精神兴奋药可导致神经生物学底物（包括单胺类物质）发生强烈而持久的变化，以及对急性药物对神经化学和行为影响的敏感性相应改变。对精神兴奋药滥用和依赖背后神经生物学机制理解的重大进展指导了药理学治疗策略以改善临床结果。特别是，功能性激动剂治疗可有效用于稳定单胺神经化学、影响行为并导致长期戒断。然而，还需要更多的临床研究来确定安全有效的药物疗法。
