Well over 72,000 Americans died of opioid overdose in 2017, with a sharp increase in 2014 – 2017 due to synthetic opioids 1, prompting a public health crisis whose biological underpinnings are poorly understood. The ¼-opioid receptor (MOR) mediates the most powerful addictive properties of abused opiates and much research has identified chemically diverse ligands of varying efficacies for pain relief or treatment of addiction. Because of its substantive role in mediating reward and positive reinforcement, the MOR is also an indirect target of alcohol, nicotine, and other drugs of abuse 2, 3. MOR-mediated synaptic alterations in reward-associated brain regions may represent a key underlying mechanism of reinforcement in drug abuse 4, but our understanding of this process in human neurons is limited.
