纽约大学Christine M. Constantinople小组取得一项新突破。他们的最新研究探明了雌激素调节奖励预测错误和强化学习。该研究于2025年11月11日发表于国际一流学术期刊《自然—神经科学》杂志上。

本研究表明，随着17β-雌二醇内源性增加，多巴胺RPEs和对先前奖励的行为敏感性增强，伏隔核核心多巴胺再摄取蛋白减少。在不同奖励状态的任务中，老鼠调整了它们启动试验的速度，平衡了努力和预期奖励。伏隔核核心多巴胺反映了影响大鼠起始时间的RPEs。较高的17β-雌二醇水平预示着对奖励状态更敏感，RPEs更高。蛋白质组学显示，17β-雌二醇升高后，多巴胺转运蛋白表达降低。最后，中脑雌激素受体的下调抑制了对奖励状态的敏感性。因此，内源性17β-雌二醇可以预测多巴胺再摄取和RPE信号，并直接指示先前奖励对行为的影响。

据介绍，性腺激素作用于整个大脑并调节精神症状。然而，激素如何影响认知过程尚不清楚。外源性17β-雌二醇是最有效的雌激素，调节伏隔核核心的多巴胺，这体现了奖励预测误差（RPEs），即收到的和期望的奖励之间的差异。

附：英文原文

Title: Estrogen modulates reward prediction errors and reinforcement learning

Author: Golden, Carla E. M., Martin, Audrey C., Kaur, Daljit, Mah, Andrew, Levy, Diana H., Yamaguchi, Takashi, Lasek, Amy W., Lin, Dayu, Aoki, Chiye, Constantinople, Christine M.

Issue&Volume: 2025-11-11

Abstract: Gonadal hormones act throughout the brain and modulate psychiatric symptoms. Yet how hormones influence cognitive processes is unclear. Exogenous 17β-estradiol, the most potent estrogen, modulates dopamine in the nucleus accumbens core, which instantiates reward prediction errors (RPEs), the difference between received and expected reward. Here we show that following endogenous increases in 17β-estradiol, dopamine RPEs and behavioral sensitivity to previous rewards are enhanced, and nucleus accumbens core dopamine reuptake proteins are reduced. Rats adjusted how quickly they initiated trials in a task with varying reward states, balancing effort against expected rewards. Nucleus accumbens core dopamine reflected RPEs that influenced rats’ initiation times. Higher 17β-estradiol predicted greater sensitivity to reward states and larger RPEs. Proteomics revealed reduced dopamine transporter expression following 17β-estradiol increases. Finally, knockdown of midbrain estrogen receptors suppressed sensitivity to reward states. Therefore, endogenous 17β-estradiol predicts dopamine reuptake and RPE signaling, and causally dictates the impact of previous rewards on behavior.

DOI: 10.1038/s41593-025-02104-z

Source: https://www.nature.com/articles/s41593-025-02104-z