Multimodal Behavioral Phenotyping Of Stress-Induced Depression-like States In Drosophila melanogaster

Metabolic, neurodegenerative, and stress-related disorders are frequently accompanied by altered locomotion, impaired decision-making, and reduced behavioral flexibility. However, accessible multimodal behavioral frameworks for quantifying these phenotypes in Drosophila melanogaster remain limited. Here, a protocol integrating forced swim exposure, Y-maze turning behavior and handedness, phototaxis, and activity assessment in the FlyVac system, open-field exploration, and long-term locomotor monitoring using the Drosophila Activity Monitor is presented. These complementary assays capture multiple dimensions of behavior, including motor output, motivation, decision structure, and behavioral variability, as functional readouts of neural and metabolic states. The pipeline is scalable, reproducible, and adaptable to pharmacological, genetic, and environmental manipulations, providing a versatile framework for detecting stress-, metabolic-, and neurodegeneration-related behavioral phenotypes in Drosophila.