A lnc6100-Mediated ceRNA Network Regulates Dopamine-Dependent Food Wanting in Honeybees

The honeybee, Apis mellifera, is a highly social and ecologically important pollinator whose foraging activity is essential for colony nutrition and survival. Food wanting is a fundamental motivational state that drives food-seeking and foraging behaviors, yet the molecular mechanisms underlying dopamine-dependent food motivation remain poorly understood. Here, we integrated transcriptomic profiling of honeybee brains (n = 120) with bioinformatic prediction to identify three candidate lncRNAs highly associated with miR-375-3p, a microRNA previously implicated in the regulation of food wanting through the dopamine synthesis pathway. Functional screening using three complementary behavioral assays then identified lnc6100 as a key regulator of food wanting. Mechanistically, dual-luciferase reporter assays confirmed that lnc6100 directly interacts with miR-375-3p. Knockdown of lnc6100 increased miR-375-3p expression, reduced Ddc expression, and decreased brain dopamine levels, indicating that lnc6100 promotes dopamine synthesis through the miR-375-3p/Ddc pathway. Furthermore, inhibition of miR-375-3p rescued the impaired food wanting, restored Ddc expression, and increased dopamine levels in lnc6100-knockdown honeybees. Together, these findings support an lnc6100–miR-375-3p–Ddc regulatory axis through which noncoding RNA interactions regulate dopamine synthesis and food wanting in honeybees. Our study reveals the molecular mechanism by which the upstream noncoding RNA that regulates dopamine-dependent food wanting, providing new insights into lncRNA-based strategies to improve honeybee colony health.