The neural circuits and signalling pathways of opioid use disorder.

The increasing prevalence of opioid use disorder (OUD) represents an important global public health crisis, often referred to as the 'opioid epidemic'. Opioids are known for their potent pain-relieving effects, but also have serious side effects, including OUD and respiratory depression, which can lead to fatal overdoses. To address this growing concern, we require a better understanding of the mechanisms underlying OUD, which typically begins with either medical or recreational opioid use and evolves into a complex and chronic brain disorder. In this Review, we highlight recent advances in our understanding of opioid receptors and the neural circuits in which they operate (including the broad network of circuits involved in reward and relief processing), focusing on the changes that follow long-term opioid exposure, abstinence and withdrawal. Additionally, we discuss recent findings that highlight the importance of the local cellular environment in shaping responses to these drugs. Overall, we aim to provide an updated overview of the field that may give us new insights into the multifaceted landscape of OUD.