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iScience· 2026Q1

Dopamine dynamics promote cooperative behavior not just the rewards accompanying cooperation

Kexin Chai, jing cai, Yizhou Zhuo, Nuo Da et al.

Short summary

Dopamine (DA) in the nucleus accumbens medial shell specifically encodes successful cooperative actions, not the rewards themselves, and this DA representation is stable after training. Low-dose blockade of D1 receptors selectively impaired cooperation by 65.9% without affecting locomotion or individual reward-seeking.

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Key points

  • Nucleus accumbens medial shell dopamine specifically encodes 1s-synchronized successful cooperative actions, not rewards or other cues.
  • Cooperation-related DA representations are asymmetrically stable, persisting after switching to individual tasks.
  • D1 receptor-mediated phasic dopamine in the nucleus accumbens is necessary for cooperative behavior.
  • Low-dose D1 receptor blockade selectively impaired cooperation success by 65.9% without affecting basal locomotion or individual reward-seeking.

AI-generated from the title and abstract; the full text is not read.

Abstract

Research Hypothesis 1.Nucleus accumbens medial shell (NAcMedSh) dopamine (DA) specifically encodes 1s-synchronized successful cooperative actions, not social contact, motor execution, reward expectation or sensory cues. 2.Learned cooperation-related DA representations have asymmetric stability: they persist after switching to individual tasks, while naive animals need de novo learning for cooperation tasks. 3.NAc D1 receptor (D1R)-mediated phasic DA is necessary for cooperative behavior, with task-specific effects: low-dose D1R blockade selectively impairs cooperation without affecting basal locomotion or individual reward-seeking. Data Acquisition Data from 2-month-old male C57BL/6J mice, approved by UESTC Animal Ethics Committee. Behavioral paradigm: 1s time-window cooperative nose-poke task; paired mice get shared water reward only if nose-pokes fall within 1s, with full control paradigms. Neural recording: AAV2-hSyn-GRABDA3m injected into NAcMedSh; fiber photometry recorded DA dynamics, 405nm reference for artifact correction. Pharmacology: Bilateral NAcMedSh cannulas for microinjection of D1R antagonist SCH23390 or saline. Behavioral data: EthoVision XT 15 recorded core behavioral metrics. Dataset Structure 6 experimental folders with raw/preprocessed fiber data and behavioral markers; 4 Prism project files for statistical analysis, inter-group comparison and dose-response analysis. Key Findings & Interpretation 1.NAc DA specifically encodes cooperative actions, not external rewards: DA AUC for successful cooperation rose significantly with training (p=0.0001), failed triggers evoked no response; reward-related DA remained stable. Reward extinction eliminated reward DA, but cooperation DA stayed stable.Interpretation: Revises classic RPE theory; NAc DA assigns intrinsic motivational value to cooperation itself. 2.Asymmetric stability of cooperation DA: Cooperation-to-independent group had stable trigger DA post-switch; independent-to-cooperation group showed full de novo DA learning.Interpretation: Learned cooperation DA is consolidated like skill memory, with behavioral inertia. 3.D1R is necessary for cooperation with task specificity: Low-dose SCH23390 reduced cooperation success by 65.9% reversibly, no effect on locomotion/individual reward-seeking.Interpretation: Cooperation has higher dependence on D1R-mediated phasic DA, providing a preclinical target for social cooperation deficits. Data Use Guidelines Interpretation rules: Core metrics: cooperation success rate, inter-nose-poke interval, event-related ΔF/F0 Z-score/AUC. Significance: *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, ns=no significant difference. Reuse: Raw data reanalyzable via MATLAB/Python; Prism files replicate all statistics. Limitations: Data from male C57BL/6J mice; cooperation defined as 1s synchronized nose-pokes, not generalizable to other scenarios.

The authors' abstract, as published at the source. iScience, 2026 · DOI ↗

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Field: Cellular and Molecular Neuroscience

Cellular and Molecular NeuroscienceNeuroscience