Effects of Transient Administration of the NMDA Receptor Antagonist MK-801 in Drosophila melanogaster Activity, Sleep, and Negative Geotaxis

MK-801, also called dizocilpine, is an N-methyl-D-aspartate (NMDA) receptor antagonist widely used in animal research to model schizophrenia-like phenotypes. Although its effects in rodents are well characterised, little is known about the outcomes of this drug in other organisms. In this study, we characterise the effects of MK-801 on the locomotion, sleep, and negative geotaxis of the fruit fly Drosophila melanogaster. We observed that acute (24 h) and chronic (7 days) administration of MK-801 enhanced negative geotaxis activity in the forced climbing assay for all tested concentrations (0.15 mM, 0.3 mM, and 0.6 mM). Moreover, acute administration, but not chronic, increased the flies' locomotion in a dose-dependent matter. Finally, average sleep duration was not affected by any concentration or administration protocol. Our results indicate that acute MK-801 could be used to model hyperactivity phenotypes in Drosophila melanogaster. Overall, this study provides further evidence that the NMDA receptor system is functionally conserved in flies, suggesting the usefulness of this model to investigate several phenotypes as a complement and replacement of the rodent models within drug discovery.

Automated summary

In this study, the effects of MK-801 on locomotion, sleep, and negative geotaxis in fruit flies were investigated. The results showed that MK-801 enhanced negative geotaxis activity and increased locomotion in a dose-dependent manner in acute administration. However, it did not affect sleep duration. This study provides further evidence for the functional conservation of the NMDA receptor system in flies and suggests the usefulness of the fruit fly model in investigating various phenotypes as an alternative to rodent models in drug discovery.