Background: Statins, including simvastatin, are widely prescribed cholesterol-lowering drugs with well-established cardiovascular benefits, yet their potential neurobehavioral effects, including sleep disturbances, remain unclear. Because sleep regulation in Drosophila melanogaster is conserved with mammals, this model provides a powerful system to investigate drug-induced behavioral changes. Given the reported neurobehavioral effects of lipophilic statins, we hypothesized that simvastatin exposure would alter sleep-wake behavior and sleep architecture in D. melanogaster.

Methods: Wild-type flies were treated with simvastatin at concentrations of 0.00 (control), 0.05, 0.5, and 1.0 mM, and behavioral phenotypes were quantified.

Results: We observed a disruption of sleep architecture: 0.05 mM produced no detectable effect; 0.5 mM induced a robust insomnia-like phenotype characterized by reduced total sleep and prolonged sleep latency; whereas 1.0 mM increased arousal, enhancing wake activity and delaying sleep onset despite preserved total sleep amount.

Conclusion: These findings demonstrate that simvastatin exerts distinct, dose-dependent effects on sleep regulation, differentially affecting sleep initiation and maintenance. Collectively, this study suggests that Drosophila may serve as a useful model for investigating the behavioral effects of simvastatin, although further studies are required to validate and extend these observations.