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Updated: Jun 24, 2025

A Conflict Model of Reward-seeking Behavior in Male Rats
Published on: February 20, 2019
A master regulator of opioid reward in the ventral prefrontal cortex
Alexander C W Smith1, Soham Ghoshal1, Samuel W Centanni2
1Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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.
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