A master regulator of opioid reward in the ventral prefrontal cortex

• 成果类型: Article
• 署名作者: Smith, Alexander C. W.; Ghoshal, Soham; Centanni, Samuel W.; Heyer, Mary P.; Corona, Alberto; Wills, Lauren; Andraka, Emma; Lei, Ye; O'Connor, Richard M.; Caligiuri, Stephanie P. B.; Khan, Sohail; Beaumont, Kristin; Sebra, Robert P.; Kieffer, Brigitte L.; Winder, Danny G.; Ishikawa, Masago; Kenny, Paul J.
• 署名单位: Icahn School of Medicine at Mount Sinai; Vanderbilt University; Icahn School of Medicine at Mount Sinai; McGill University; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Lorraine; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Medical University of South Carolina; Wake Forest University; University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9978
• DOI: 10.1126/science.adn0886
• 发表日期: 2024-06-07
• 关键词: conditioned place preference; parabrachial nucleus; morphine; dopamine; heroin; opiate; receptor; neurons; brain; projections

摘要

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express mu-opioid receptors (mu ORs). Disrupting mu OR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.