Abstract
Food wanting in honeybees is closely associated with the neurotransmitter dopamine; however, the regulatory role of non-coding RNAs in this process remains unclear. In this study, using the honeybee (Apis mellifera) as a model organism, we systematically investigated the molecular network and functional mechanisms by which long non-coding RNAs (lncRNAs) regulate the dopaminergic signaling pathway to mediate food wanting. By establishing two appetite-state models, fed honeybees (FB) and starved honeybees (SB), and combining brain dopamine quantification with behavioral assays, we found that dopamine levels in the honeybee brain were significantly elevated during starvation. Using transcriptome sequencing, we identified 1146 lncRNAs in the honeybee brain, among which 174 were differentially expressed long noncoding RNAs (DElncRNAs) between the two states, predominantly upregulated. Cis- and trans-acting analyses revealed that these DElncRNAs could target multiple genes involved in neural signal transmission, synaptic function, and dopaminergic pathways. KEGG enrichment analysis showed that their target genes were significantly enriched in pathways such as taste transduction, dopaminergic synapse, and neuroactive ligand-receptor interaction. Furthermore, a ceRNA network revealed that several DElncRNAs may regulate dopamine synthesis genes, including DOPA decarboxylase (Ddc), by competing for dopamine-associated miRNAs such as miR-375-3p, influencing food wanting in honeybees. Overall, our findings provide a foundation for uncovering the potential regulatory mechanisms of DElncRNAs in honeybee food wanting and offer new insights into the connection between neural regulation and behavioral manifestation in insects.