2025年11月20日，波士顿儿童医院Michael A. Crickmore研究团队在《自然—神经科学》杂志发表论文，报道了局部对多巴胺的抵抗导致行为贬值。

研究团队以果蝇为主题来研究这种常见的动机变化形式，发现先前的交配使雄性在受到挑战时更有可能放弃未来的交配。

在这里，该研究团队表明，在交配过程中，多巴胺通过D2样受体（D2R）发出信号，以促进对挑战的适应能力，否则可能会促使雄性改变行为。这种激励多巴胺信号抑制了交配决策神经元（CDNs）的输出，当它们超过阈值时，CDNs可以截断交配。重复诱导的交配贬值是由于β-抑制蛋白依赖的D2R对CDNs的脱敏，使它们暂时抵抗自然释放或实验提供的多巴胺。当局部对多巴胺的脱敏被阻止时，雄性没有表现出疲劳的迹象，把每一次交配都当作是第一次。这些发现解释了一个广泛的动机现象，并揭示了D2R对药物诱导脱敏的臭名昭著的敏感性的自然功能。

据悉，重复的经历会导致行为特异性疲劳。

附：英文原文

Title: Behavioral devaluation by local resistance to dopamine

Author: Miner, Lauren E., Gautham, Aditya K., Crickmore, Michael A.

Issue&Volume: 2025-11-20

Abstract: Repeated experiences can cause behavior-specific fatigue. We use Drosophila to study this common form of motivational change, finding that prior matings make males more likely to abandon future copulations when challenged. Here we show that, during mating, dopamine signals through the D2-like receptor (D2R) to promote resilience to challenges that might otherwise cause the male to switch behaviors. This motivating dopamine signal suppresses the output of the copulation decision neurons (CDNs), which can truncate matings when pushed past threshold. Repetition-induced devaluation of mating results from β-arrestin-dependent desensitization of the D2R on the CDNs, rendering them temporarily resistant to naturally released or experimentally supplied dopamine. When local desensitization to dopamine is prevented, the male shows no signs of fatigue, treating each mating as if it were his first. These findings explain a widespread motivational phenomenon and reveal a natural function for the notorious susceptibility of the D2R to drug-induced desensitization.

DOI: 10.1038/s41593-025-02079-x

Source: https://www.nature.com/articles/s41593-025-02079-x