School of Biological Sciences, Illinois State University, Normal, IL 61790-4120, USA.
Department of Psychology, University of Illinois at Chicago, Chicago, IL 60607-7137, USA.
Trends Neurosci. 2014 Apr;37(4):200-10. doi: 10.1016/j.tins.2014.02.002. Epub 2014 Mar 20.
Phasic increases in brain dopamine are required for cue-directed reward seeking. Although compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyperactivating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyperactivation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural rewards and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome.
大脑多巴胺的阶段性增加是线索导向的奖励寻求所必需的。虽然在食欲行为的框架内具有说服力，但非法药物通过过度激活这些多巴胺瞬变来劫持奖励回路的观点与既定的精神兴奋剂药理学不一致。然而，最近将安非他命（AMPH）、可卡因和其他成瘾性多巴胺转运蛋白抑制剂（DAT-Is）重新分类的工作支持将短暂的过度激活作为滥用药物的统一假设。我们在这里认为，重新分类还确定了多巴胺神经元产生爆发式放电作为关键作用。与被感觉系统处理的自然奖励不同，药物直接作用于大脑。因此，为了模仿自然奖励并利用奖励回路，必须重新产生多巴胺瞬变。在可用的药物靶点中，只有爆发式放电才能实现这一必要的结果。
