Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Nat Rev Neurosci. 2020 Nov;21(11):625-643. doi: 10.1038/s41583-020-0378-z. Epub 2020 Oct 6.
Critical features of human addiction are increasingly being incorporated into complementary animal models, including escalation of drug intake, punished drug seeking and taking, intermittent drug access, choice between drug and non-drug rewards, and assessment of individual differences based on criteria in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Combined with new technologies, these models advanced our understanding of brain mechanisms of drug self-administration and relapse, but these mechanistic gains have not led to improvements in addiction treatment. This problem is not unique to addiction neuroscience, but it is an increasing source of disappointment and calls to regroup. Here we first summarize behavioural and neurobiological results from the animal models mentioned above. We then propose a reverse translational approach, whose goal is to develop models that mimic successful treatments: opioid agonist maintenance, contingency management and the community-reinforcement approach. These reverse-translated 'treatments' may provide an ecologically relevant platform from which to discover new circuits, test new medications and improve translation.
人类成瘾的关键特征越来越多地被纳入补充性动物模型中，包括药物摄入的增加、受惩罚的药物寻求和摄取、间歇性药物获取、药物和非药物奖励之间的选择，以及根据精神障碍诊断与统计手册第四版 (DSM-IV) 的标准评估个体差异。这些模型结合新技术，提高了我们对药物自我给药和复发的大脑机制的理解，但这些机制上的进展并没有带来成瘾治疗的改善。这个问题不仅存在于成瘾神经科学中，而且越来越令人失望，需要重新分组。在这里，我们首先总结了上述动物模型的行为和神经生物学结果。然后，我们提出了一种反向翻译方法，其目标是开发模仿成功治疗方法的模型：阿片类激动剂维持治疗、条件管理和社区强化方法。这些反向翻译的“治疗”可能为发现新的回路、测试新的药物和改善翻译提供一个具有生态相关性的平台。
