Pharmacological characterization of the forced swim test in Drosophila melanogaster.

The forced swim test is commonly used as a preclinical screen of antidepressant medication efficacy in rats and mice. Neckameyer and Nieto-Romero (Stress 18:254-66, 2015) adopted the forced swim test for use with the fruit fly Drosophila melanogaster and showed that behavior in this test is sensitive to several physiologically relevant stressors. However, whether this test might be sensitive to the effects of antidepressant medications or other compounds is unknown. In the current studies, we fed drugs to male and female flies that we expected to either decrease or increase the duration of immobility in the forced swim test, including fluoxetine, desipramine, picrotoxin, reserpine, 3-iodo-tyrosine, and ethanol. Fluoxetine was the only drug tested that affected behavior in this test, and surprisingly, the direction of the effect depended on the duration of feeding. Short-term (30 min) feeding of the drug prior to test resulted in the expected increase in latency to immobility, while a longer feeding duration (20-24 h) decreased this measure. These results suggest that the pharmacological profile of the fly FST is more restricted than that of the rat or mouse FST, and that the duration of drug exposure is an important consideration in pharmacological research using flies.