Reduced serotonergic transmission alters sensitivity to cost and reward via 5-HT1A and 5-HT1B receptors in monkeys.

Autor: Hori Y; Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, Japan., Mimura K; Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, Japan.; Research Center for Medical and Health Data Science, The Institute of Statistical Mathematics, Tokyo, Japan., Nagai Y; Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, Japan., Hori Y; Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, Japan., Kumata K; Department of Advanced Nuclear Medicine Sciences, National Institutes for Quantum Science and Technology, Chiba, Japan., Zhang MR; Department of Advanced Nuclear Medicine Sciences, National Institutes for Quantum Science and Technology, Chiba, Japan., Suhara T; Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, Japan., Higuchi M; Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, Japan., Minamimoto T; Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, Japan.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2024 Jan 01; Vol. 22 (1), pp. e3002445. Date of Electronic Publication: 2024 Jan 01 (Print Publication: 2024).
DOI: 10.1371/journal.pbio.3002445
Abstrakt: Serotonin (5-HT) deficiency is a core biological pathology underlying depression and other psychiatric disorders whose key symptoms include decreased motivation. However, the exact role of 5-HT in motivation remains controversial and elusive. Here, we pharmacologically manipulated the 5-HT system in macaque monkeys and quantified the effects on motivation for goal-directed actions in terms of incentives and costs. Reversible inhibition of 5-HT synthesis increased errors and reaction times on goal-directed tasks, indicating reduced motivation. Analysis found incentive-dependent and cost-dependent components of this reduction. To identify the receptor subtypes that mediate cost and incentive, we systemically administered antagonists specific to 4 major 5-HT receptor subtypes: 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4. Positron emission tomography (PET) visualized the unique distribution of each subtype in limbic brain regions and determined the systemic dosage for antagonists that would achieve approximately 30% occupancy. Only blockade of 5-HT1A decreased motivation through changes in both expected cost and incentive; sensitivity to future workload and time delay to reward increased (cost) and reward value decreased (incentive). Blocking the 5-HT1B receptor also reduced motivation through decreased incentive, although it did not affect expected cost. These results suggest that 5-HT deficiency disrupts 2 processes, the subjective valuation of costs and rewards, via 5-HT1A and 5-HT1B receptors, thus leading to reduced motivation.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Hori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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