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<p>Addicted individuals prefer drug rewards over natural rewards. Dysregulated dopamine (DA) signaling in the nucleus accumbens is thought to trigger this phenomenon, but there is little supporting evidence. Using a genetically encoded sensor, we monitored DA dynamics in mice in an operant associative task with natural (fat solution) or artificial (cocaine or optogenetic DA self-stimulation) rewards. During learning, DA transients emerged at predictive cues for both reward types, vanished at natural reward delivery, but persisted at artificial reward delivery. In choice sessions, animals’ preferences varied from exclusive natural reward to exclusive artificial reward. Individual preferences were predicted by cue-evoked DA response magnitudes. Revaluation of reward contingencies shifted reward-type preference and DA signaling accordingly, but not in mice showing compulsive drug seeking, indicating impaired value updating in these mice. These results support a model in which DA drives adaptive reward seeking, with persistent cue-associated DA signaling underpinning addiction vulnerability.</p>

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Conditioned accumbal dopamine transients forecast individual preference for drug versus natural rewards and compulsive behavior

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月26日

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  • Vincent Pascoli,
  • Laurena Python,
  • Agnès Hiver,
  • Ruud van Zessen,
  • Fabrice Chaudun,
  • Julian Hinz,
  • Jérôme Flakowski,
  • Benoit Girard,
  • Maria Reva,
  • Camilla Bellone,
  • Vahid Esmaeili,
  • Christian Lüscher

摘要

Addicted individuals prefer drug rewards over natural rewards. Dysregulated dopamine (DA) signaling in the nucleus accumbens is thought to trigger this phenomenon, but there is little supporting evidence. Using a genetically encoded sensor, we monitored DA dynamics in mice in an operant associative task with natural (fat solution) or artificial (cocaine or optogenetic DA self-stimulation) rewards. During learning, DA transients emerged at predictive cues for both reward types, vanished at natural reward delivery, but persisted at artificial reward delivery. In choice sessions, animals’ preferences varied from exclusive natural reward to exclusive artificial reward. Individual preferences were predicted by cue-evoked DA response magnitudes. Revaluation of reward contingencies shifted reward-type preference and DA signaling accordingly, but not in mice showing compulsive drug seeking, indicating impaired value updating in these mice. These results support a model in which DA drives adaptive reward seeking, with persistent cue-associated DA signaling underpinning addiction vulnerability.