英国牛津大学Scott Waddell等研究人员合作发现，多巴胺能系统忽略不良后果去寻求奖励。2023年10月25日，《自然》杂志在线发表了这项成果。
研究人员描述了在黑腹果蝇中产生不顾不良后果寻求奖励行为的多巴胺能神经机制。气味配以光遗传激活特定的编码奖励的多巴胺能神经元亚群，成为饥饿果蝇在忽略食物和忍受电击惩罚时寻求奖赏的线索。在对糖进行学习或对其他多巴胺能神经元群进行合成激活后，并没有观察到无限制地寻求奖励的现象。奖励编码多巴胺能神经元和惩罚编码多巴胺能神经元之间的拮抗作用解释了雌蝇在遭受惩罚后仍坚持寻求奖励的原因，而奖励编码多巴胺能神经元的合成参与也损害了多巴胺能对可用食物的普通需求依赖性评估。
连接组分析表明，编码奖励的多巴胺能神经元群接受高度异质的输入，这与并行表征不同奖励是一致的，而且记录显示了特定状态门控和饱食相关信号。研究人员认为，类似的多巴胺能估价系统功能障碍也可能导致哺乳动物不适应性地寻求奖励。
据介绍，寻求资源的行为通常受到生理需求和危险威胁的限制，失去这些控制与病态寻求奖赏有关。虽然已知大脑多巴胺能评价系统的功能障碍会导致无约束的奖赏寻求，但这种行为的根本原因尚不清楚。
附：英文原文
Title: Dopaminergic systems create reward seeking despite adverse consequences
Author: Jovanoski, Kristijan D., Duquenoy, Lucille, Mitchell, Jessica, Kapoor, Ishaan, Treiber, Christoph D., Croset, Vincent, Dempsey, Georgia, Parepalli, Sai, Cognigni, Paola, Otto, Nils, Felsenberg, Johannes, Waddell, Scott
Issue&Volume: 2023-10-25
Abstract: Resource-seeking behaviours are ordinarily constrained by physiological needs and threats of danger, and the loss of these controls is associated with pathological reward seeking1. Although dysfunction of the dopaminergic valuation system of the brain is known to contribute towards unconstrained reward seeking2,3, the underlying reasons for this behaviour are unclear. Here we describe dopaminergic neural mechanisms that produce reward seeking despite adverse consequences in Drosophila melanogaster. Odours paired with optogenetic activation of a defined subset of reward-encoding dopaminergic neurons become cues that starved flies seek while neglecting food and enduring electric shock punishment. Unconstrained seeking of reward is not observed after learning with sugar or synthetic engagement of other dopaminergic neuron populations. Antagonism between reward-encoding and punishment-encoding dopaminergic neurons accounts for the perseverance of reward seeking despite punishment, whereas synthetic engagement of the reward-encoding dopaminergic neurons also impairs the ordinary need-dependent dopaminergic valuation of available food. Connectome analyses reveal that the population of reward-encoding dopaminergic neurons receives highly heterogeneous input, consistent with parallel representation of diverse rewards, and recordings demonstrate state-specific gating and satiety-related signals. We propose that a similar dopaminergic valuation system dysfunction is likely to contribute to maladaptive seeking of rewards by mammals.
DOI: 10.1038/s41586-023-06671-8
Source: https://www.nature.com/articles/s41586-023-06671-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
