Wanhao Chi, Wenqin Fu, Cristianne R M Frazier, Liwen Xu, Jeff A Beeler, Xiaoxi Zhuang
Dopamine plays central roles in reinforcement learning and motivation, allowing animals to evaluate energetic costs and gains for efficient foraging. However, how genetic variation in dopaminergic function influences survival remains poorly understood. Here, we used Drosophila melanogaster, an established model for studying fitness, to investigate the effects of hyperdopaminergic state on survival in energetically limited environments. We used the well-characterized dopamine transporter mutant fumin (DATfmn), thermogenetic activation and pharmacological manipulations to alter dopamine signalling. In free-feeding environment, DATfmn mutants displayed normal food consumption and survival. However, in a foraging environment with energetic scarcity, DATfmn mutants exhibited reduced meal frequency and impaired survival compared with controls. Dopaminergic contribution to survival was further supported by data from genetic rescue, pharmacological rescue and thermogenetic activation. Because dopamine modulates both learning and exploration-exploitation bias, we dissociated these processes experimentally. Amphetamine treatment during the post-learning phase, but not during learning, impaired survival, indicating that exploration-exploitation bias after learning, rather than impaired learning, accounts for the observed phenotype. Moreover, DATfmn flies showed increased exploratory activity and reduced exploitation of known food sources. These results demonstrate that hyperdopaminergic state disrupts the balance between exploration and exploitation, thereby compromising survival under conditions of limited energy availability.