miR-375-3p regulates food wanting in honeybees by mediating the dopamine synthesis pathway

Transient dopaminergic signaling activation in the honeybee brain regulates food wanting and drives foraging behavior. However, the roles of endogenous microRNAs (miRNAs) in the regulation of food wanting by dopamine pathways remain poorly understood. Here, we report that miR-375-3p plays a critical role in the food-wanting system in honeybees. MicroRNA transcriptomic analysis revealed the marked downregulation of miR-375-3p expression in the brains of starved foragers, which exhibited increased appetitive responsiveness. Furthermore, miR-375-3p directly targeted DOPA decarboxylase (Ddc), a crucial enzyme in dopamine synthesis, thereby decreasing dopamine levels. Overexpression of miR-375-3p or Ddc RNA interference reduced dopamine production and suppressed food wanting in honeybees. Collectively, the results indicate that miR-375-3p acts as a negative regulator of food wanting by inhibiting Ddc expression and reducing dopamine-mediated appetitive behavior. This study reveals a molecular mechanism underlying miRNA-regulated food wanting and suggests potential strategies for miRNA-based intervention in managing honeybee health.