Large Drosophila panel study maps genetic variation underlying cocaine consumption and preference

Understanding the genetic architecture of cocaine use disorder (CUD) in human populations is complicated by environmental confounding, ascertainment bias, and the difficulty of controlled experimentation. A preprint posted to bioRxiv on 22 August 2026 exploits the tractability of *Drosophila melanogaster* to address these questions at scale.

The authors assessed cocaine consumption and cocaine preference across 74,875 flies derived from 598 sequenced, wild-derived, inbred lines belonging to the expanded Drosophila melanogaster Genetic Reference Panel (DGRP3). The study identified significant broad-sense heritability for both traits, as well as sexual dimorphism — with male and female flies showing different response profiles — and genetic variation in the degree of that dimorphism across lines. Notably, the majority of lines exhibited cocaine avoidance, while approximately 10% showed preference, mirroring patterns seen in human epidemiological data where only a subset of individuals who use cocaine develop a use disorder.

The DGRP3 resource enables genome-wide association analyses within an isogenic, fully sequenced framework, allowing candidate loci to be identified without the population stratification that complicates human GWAS. The findings complement a cluster published in Genetic Current on 9 August 2026 reporting a GWAS in heterogeneous stock rats for cocaine aversion, collectively illustrating the value of invertebrate and rodent models in dissecting addiction genetics. As a preprint, these findings have not yet undergone peer review.