Rules of disengagement: orexin-arousal and dopamine-utility as separable axes
- 1ETH Zurich
Abstract
Staying on task, leaving it, and coming back to it are processes we experience daily. They depend on task utility and arousal, but the neurochemical processes behind this interplay are unknown. In mice performing a decision-making task with shifting reward size, we identified latent engagement states and the transitions between them. Pupil-linked arousal and dopaminergic utility coding predicted these transitions along separable axes. Orexin antagonism with almorexant disengaged mice at low reward, an effect mediated by pupil-linked arousal and not by dopamine. GLP-1 receptor agonism with semaglutide reduced the gain with which accumbal dopamine integrates reward history, which predicted the progressive disengagement it caused, with no detectable contribution from arousal or orexin. Fast striatal and slow accumbal dopamine codes predicted engagement on their own timescales. These results decouple orexin-driven arousal from dopamine-mediated utility coding in task engagement, with implications for two widely used drug classes and for disorders of motivation.
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BibTeX
@misc{grujic2026rules,
title = {{Rules of disengagement: orexin-arousal and dopamine-utility as separable axes}},
author = {N. Grujic and V. I. Ploerer and M. Hamann and A. Tesmer and E. Bracey and D. Peleg-Raibstein and D. Burdakov},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.25.761642},
url = {https://www.biorxiv.org/content/10.64898/2026.10.25.761642v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Rules of disengagement: orexin-arousal and dopamine-utility as separable axes
AU - N. Grujic
AU - V. I. Ploerer
AU - M. Hamann
AU - A. Tesmer
AU - E. Bracey
AU - D. Peleg-Raibstein
AU - D. Burdakov
PY - 2026
DA - 2026/10/25
PB - bioRxiv
DO - 10.64898/2026.10.25.761642
UR - https://www.biorxiv.org/content/10.64898/2026.10.25.761642v1
AB - Staying on task, leaving it, and coming back to it are processes we experience daily. They depend on task utility and arousal, but the neurochemical processes behind this interplay are unknown. In mice performing a decision-making task with shifting reward size, we identified latent engagement states and the transitions between them. Pupil-linked arousal and dopaminergic utility coding predicted these transitions along separable axes. Orexin antagonism with almorexant disengaged mice at low reward, an effect mediated by pupil-linked arousal and not by dopamine. GLP-1 receptor agonism with semaglutide reduced the gain with which accumbal dopamine integrates reward history, which predicted the progressive disengagement it caused, with no detectable contribution from arousal or orexin. Fast striatal and slow accumbal dopamine codes predicted engagement on their own timescales. These results decouple orexin-driven arousal from dopamine-mediated utility coding in task engagement, with implications for two widely used drug classes and for disorders of motivation.
ER -