Genetic mouse models in opioid research: current status and future directions.

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.