Synthetic and semi-synthetic opioids are prescribed for the management of severe pain conditions, but their long-term use is often leading to physical dependence and addiction disorders. Understanding the complex neurobiology of the opioid system in preclinical models will be essential for the development of safe and efficacious analgesics. With rising numbers of synthetic opioid users and overdose cases, a better understanding of the neuroanatomical and cellular pathways associated with physical dependence and addiction is expected to guide treatment approaches for opioid use disorders. In this commentary, we highlight the importance of advanced genetic mouse models for studying the regional effects of opioid receptors, and we discuss the need of genetic mouse models for the investigation of the regional, circuit and cell compartment-specific role of intracellular mediators of opioid actions.

合成和半合成阿片类药物用于治疗严重疼痛，但长期使用往往会导致身体依赖和成瘾障碍。了解临床前模型中阿片类药物系统的复杂神经生物学对于开发安全有效的镇痛药至关重要。随着合成阿片类药物使用者和过量病例数量的不断增加，更好地了解与身体依赖和成瘾相关的神经解剖学和细胞通路有望指导阿片类药物使用障碍的治疗方法。在这篇评论中，我们强调了先进的基因小鼠模型对于研究阿片受体的区域效应的重要性，并讨论了基因小鼠模型对于研究阿片类药物细胞内介质的区域、回路和细胞区室特异性作用的需求行动。