London E D
Brain Research Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, United States.
Adv Pharmacol. 2016;76:67-84. doi: 10.1016/bs.apha.2016.01.002. Epub 2016 Mar 2.
The nonmedical use of amphetamine-type stimulants is a worldwide problem, with substantial medical and social consequences. Nonetheless, the identification of a pharmacological treatment for amphetamine use disorder remains elusive. Stimulant users exhibit neurochemical evidence of dopamine-system dysfunction as well as impulsive behaviors that may interfere with the success of treatments for their addiction. This review focuses on the potential role of dopaminergic neurotransmission in impulsivity, both in healthy individuals and chronic stimulant users who meet criteria for methamphetamine dependence. Presented are findings related to the potential contributions of signaling through dopamine D1- and D2-type receptors to self-control impulsivity in methamphetamine- dependent users. The information available points to signaling through striatal D2-type dopamine receptors as a potential therapeutic target for stimulant use disorders, but medications that target D2-type dopamine receptors have not been successful in treating stimulant-use disorders, possibly because D2-type receptors are downregulated. Other means to augment D2-type receptor signaling are therefore under consideration, and one promising approach is the addition of exercise training as an adjunct to behavioral treatment for addiction.
苯丙胺类兴奋剂的非医疗使用是一个全球性问题，会带来严重的医学和社会后果。尽管如此，尚未找到针对苯丙胺使用障碍的药物治疗方法。兴奋剂使用者表现出多巴胺系统功能障碍的神经化学证据以及可能干扰其成瘾治疗成功的冲动行为。本综述重点关注多巴胺能神经传递在冲动性方面的潜在作用，这在健康个体以及符合甲基苯丙胺依赖标准的慢性兴奋剂使用者中均有体现。文中呈现了与通过多巴胺D1型和D2型受体信号传导对甲基苯丙胺依赖使用者自我控制冲动性的潜在贡献相关的研究结果。现有信息表明，纹状体D2型多巴胺受体信号传导可能是兴奋剂使用障碍的潜在治疗靶点，但针对D2型多巴胺受体的药物在治疗兴奋剂使用障碍方面并不成功，可能是因为D2型受体下调。因此，正在考虑其他增强D2型受体信号传导的方法，一种有前景的方法是将运动训练作为成瘾行为治疗的辅助手段。
