Johnny Bee Good: Bees as Models to Study the Hijacking of the Reward System

摘要 大脑中调节我们感知奖赏的回路统称为“奖赏系统”，它将快乐与生活必需品--食物和生殖--联系在一起。奖励制度也是我们社会中一些最悲惨、最有害、最昂贵的行为的根源。这些包括滥用药物成瘾，肥胖相关行为，危险的寻求刺激行为，以及反常的性行为。我对蜜蜂的利他主义行为进行的研究让我对奖励系统有了新的见解。我发现，在独居昆虫中调节自私行为的神经化学系统也在调节高度社会化的蜜蜂的利他行为，我得出的结论是，在如上所述的一生中，奖赏系统不仅容易受到“劫持”--耦合到具有负面后果的刺激--的影响，而且在进化过程中也容易受到劫持。我建议使用组学技术(高通量测序、转录组学、表观基因组学、蛋白质组学和代谢组学)从分子方面了解如何从自私行为到利他行为来“翻转”奖赏系统。这些分析将在精心挑选的一组密切相关的蜜蜂物种上进行，其中一些是社会性的(有利他行为)，另一些是孤独的(没有)。从系统生物学、神经科学和进化生物学的这种新颖的综合中获得的见解将改变我们对药物成瘾和其他奖赏系统疾病的理解，并为新的治疗干预形式提供基础。

Abstract The circuits in the brain that mediate our perception of reward, known collectively as the "reward system," couple pleasure with the essentials of life: food and reproduction. The reward system also lies at the root of some of the most tragic, harmful, and costly behaviors in our society. These include addiction to substances of abuse, obesity-related behavior, dangerous thrill seeking behavior, and aberrant sexual behavior. Research that I performed on altruistic behavior in honey bees has led me to a new insight about the reward system. Finding that the same neurochemical system that modulates selfish behavior in solitary insects modulates altruistic behavior in the highly social honey bee, I conclude that not only is the reward system vulnerable to "hijacking"- -coupling to stimuli with negative consequences-- over the course of a lifetime as mentioned above, but it also is vulnerable to hijacking in evolutionary time. I propose to use 'omic technologies (high-throughput sequencing, transcriptomics, epigenomics, proteomics, and metabolomics) to understand in molecular terms how to "flip" the reward system, from selfish to altruistic behavior. These analyses will be performed on a carefully selected set of closely related species of bees, some social (with altruistic behavior) and some solitary (without). The insights gained from this novel synthesis of systems biology, neuroscience, and evolutionary biology will transform our understanding of drug addiction and other diseases of the reward system and provide the foundation for new forms of therapeutic intervention.