A master regulator of opioid reward in the ventral prefrontal cortex.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38843332.
- Also identified by DOI 10.1126/science.adn0886 and PMC identifier 11323237.
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Abstract
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 μ-opioid receptors (μORs). Disrupting μOR 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.
Medical subject headings
- Analgesics, Opioid
- Opioid-Related Disorders
- Oxycodone
- Parabrachial Nucleus
- Prefrontal Cortex
- Receptors, Opioid, mu
- Reward
- Avoidance Learning