A Brief Overview of Ethanol Tolerance and Its Potential Association with Circadian Rhythm in Drosophila

Alcohol consumption and addiction remain global health concerns, with significant loss of productivity, morbidity, and mortality. Drosophila melanogaster, a widely used model organism, offers valuable insights into the genetic and neuronal mechanisms underlying ethanol-induced behaviors (EIBs) such as sedation, recovery, and tolerance. This narrative review focuses on studies in the Drosophila model system suggesting an association between circadian rhythm genes as modulators of ethanol tolerance. Mutations in these genes disrupt both the circadian cycle and tolerance, underscoring the interplay between circadian rhythm and ethanol processing although the exact mechanisms remain largely unknown. Additionally, genes involved in stress response, gene expression regulation, neurotransmission, and synaptic activity were implicated in ethanol tolerance modulation. At the neuronal level, recent studies have highlighted the involvement of corazonin (CRZ) and neuropeptide F (NPF) neurons in modulating EIBs. Understanding the temporal dynamics of tolerance development is crucial for describing the molecular basis of ethanol tolerance. Ultimately, insights gained from Drosophila studies hold promise for elucidating the neurobiological underpinnings of alcohol use disorders and addiction, contributing to more effective interventions and treatments.