Silencing of CYP4C61 disrupts dopamine metabolism and impairs adaptation to resistant rice in the virulent brown planthopper (Nilaparvata lugens)
while the adaptation of pest insects to resistance limits the efficiency of resistant rice varieties. The cytochrome P450 gene CYP4C61 was previously identified as a key locus underlying brown planthopper (BPH, Nilaparvata lugens) adaptation to the resistant rice variety IR36, but its metabolic function remained unknown. Here, we integrated RNAi-mediated gene silencing, untargeted metabolomics, and transcriptomics to elucidate the metabolic role of CYP4C61 in the BPH population virulent to resistant rice IR36. CYP4C61 silencing significantly impaired BPH fitness, including reduced body weight, increased mortality, disrupted feeding behavior, and progressive body darkening on IR36 rice. Metabolomic analysis identified 240 differentially abundant metabolites in silenced BPH on IR36, revealing a pattern of precursor reduction and product accumulation in the dopamine pathway. Transcriptomic analysis also revealed CYP4C61 knockdown altered gene expression in dopamine pathway in a host-dependent manner. Enzyme-linked immunosorbent assay validated dopamine accumulation after CYP4C61 knockdown exclusively in the IR36 background. We demonstrate that CYP4C61 maintains dopamine homeostasis in the virulent BPH, providing the mechanistic link between a P450 gene and dopamine-mediated insect adaptation to resistant host plants.