Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Trends Neurosci. 2021 Jul;44(7):516-526. doi: 10.1016/j.tins.2021.03.003. Epub 2021 Apr 20.
Repeated drug use can change dopamine (DA) function in ways that promote the development and persistence of addiction, but in what direction? By one view, drug use blunts DA neurotransmission, producing a hypodopaminergic state that fosters further drug use to overcome a DA deficiency. Another view is that drug use enhances DA neurotransmission, producing a sensitized, hyperdopaminergic reaction to drugs and drug cues. According to this second view, continued drug use is motivated by sensitization of drug 'wanting'. Here we discuss recent evidence supporting the latter view, both from preclinical studies using intermittent cocaine self-administration procedures that mimic human patterns of use and from related human neuroimaging studies. These studies have implications for the modeling of addiction in the laboratory and for treatment.
反复使用药物会改变多巴胺（DA）的功能，从而促进成瘾的发展和持续，但方向如何？有一种观点认为，药物使用会使 DA 神经传递变钝，产生低多巴胺能状态，从而促使进一步使用药物来克服 DA 缺乏。另一种观点是，药物使用会增强 DA 神经传递，对药物和药物线索产生敏感的、超多巴胺能反应。根据第二种观点，持续使用药物是由药物“渴望”的敏化所驱动的。在这里，我们讨论了支持后一种观点的最新证据，这些证据来自使用模拟人类使用模式的间歇性可卡因自我给药程序的临床前研究，以及相关的人类神经影像学研究。这些研究对实验室中成瘾的建模和治疗具有重要意义。
