Dopamine Agonists in Parkinson's Disease Decouple Risk-Taking from Reward-Paired Cues by Enhancing Risky Choice in Their Absence
- 1West Virginia University
Abstract
Background: Common side effects of dopamine replacement therapy (DRT) for Parkinson's Disease (PD) are addiction-like impulse control disorders, including compulsive gambling. Gambling products such as slot machines prominently feature reward-paired audiovisual stimuli, which can promote riskier choices on laboratory gambling tasks in both humans and rodents. In rats, risky decision making in the presence of reward-paired cues is dependent on dopamine D3 receptor activity and is increased by ropinirole, a D2/3 receptor agonist with a higher affinity for D3 receptors. In humans, it remains uncertain whether cue-induced risky choice is amplified by dopamine agonism. Methods: We tested effects of DRT on cue-induced risky choice in 62 patients with PD (34 on levodopa monotherapy, 27 on levodopa and dopamine agonists). Patients performed two versions of a risky decision-making task: one with and one without reward-paired sensory cues, both ON and OFF DRT. A group of 36 age-matched controls completed the same task versions without DRT. Results: Across all groups, participants made riskier choices when the task included reward-paired sensory cues. Levodopa monotherapy did not affect risky decision-making. However, a combination of levodopa and dopamine agonists increased risky choices specifically in the uncued version of the task, making performance indistinguishable from that on the cued task. Conclusions: Dopamine agonists combined with levodopa promote risk-taking even in the absence of reward-paired cues. This could translate into risky reward-seeking behaviors that are decoupled from contextual factors.
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BibTeX
@misc{muksuris2026dopamine,
title = {{Dopamine Agonists in Parkinson's Disease Decouple Risk-Taking from Reward-Paired Cues by Enhancing Risky Choice in Their Absence}},
author = {K. Muksuris and E. Flynn and T. L. Feng and P. Surathi and S. C. Yeung and L. Mortazavi and A. Isberg and M. McKeown and S. Appel-Cresswell and C. A. Winstanley and A. J. Stoessl and J. Barton and M. V. Cherkasova},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.05.748022},
url = {https://www.biorxiv.org/content/10.64898/2026.09.05.748022v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Dopamine Agonists in Parkinson's Disease Decouple Risk-Taking from Reward-Paired Cues by Enhancing Risky Choice in Their Absence
AU - K. Muksuris
AU - E. Flynn
AU - T. L. Feng
AU - P. Surathi
AU - S. C. Yeung
AU - L. Mortazavi
AU - A. Isberg
AU - M. McKeown
AU - S. Appel-Cresswell
AU - C. A. Winstanley
AU - A. J. Stoessl
AU - J. Barton
AU - M. V. Cherkasova
PY - 2026
DA - 2026/09/05
PB - bioRxiv
DO - 10.64898/2026.09.05.748022
UR - https://www.biorxiv.org/content/10.64898/2026.09.05.748022v1
AB - Background: Common side effects of dopamine replacement therapy (DRT) for Parkinson's Disease (PD) are addiction-like impulse control disorders, including compulsive gambling. Gambling products such as slot machines prominently feature reward-paired audiovisual stimuli, which can promote riskier choices on laboratory gambling tasks in both humans and rodents. In rats, risky decision making in the presence of reward-paired cues is dependent on dopamine D3 receptor activity and is increased by ropinirole, a D2/3 receptor agonist with a higher affinity for D3 receptors. In humans, it remains uncertain whether cue-induced risky choice is amplified by dopamine agonism. Methods: We tested effects of DRT on cue-induced risky choice in 62 patients with PD (34 on levodopa monotherapy, 27 on levodopa and dopamine agonists). Patients performed two versions of a risky decision-making task: one with and one without reward-paired sensory cues, both ON and OFF DRT. A group of 36 age-matched controls completed the same task versions without DRT. Results: Across all groups, participants made riskier choices when the task included reward-paired sensory cues. Levodopa monotherapy did not affect risky decision-making. However, a combination of levodopa and dopamine agonists increased risky choices specifically in the uncued version of the task, making performance indistinguishable from that on the cued task. Conclusions: Dopamine agonists combined with levodopa promote risk-taking even in the absence of reward-paired cues. This could translate into risky reward-seeking behaviors that are decoupled from contextual factors.
ER -