Pharmacological characterization of the forced swim test in Drosophila melanogaster
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ORIGINAL ARTICLE
Pharmacological characterization of the forced swim test in Drosophila melanogaster Aryana R. Rasti1 · Victoria E. Coombe1 · Jerica R. Muzik1 · Christopher L. Kliethermes1 Received: 2 June 2020 / Accepted: 30 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords Depression · Forced swim test · Fluoxetine · Invertebrate · Stress
Introduction The forced swim test (FST) is commonly used in rats and mice to detect behavioral effects of putative antidepressant medications. In a typical experiment, an experimentally naïve animal is placed into an inescapable container of water and the amount of time spent actively swimming (struggling) during a brief session is recorded. Acute administration of clinically effective antidepressants such as fluoxetine, citalopram, or paroxetine tends to increase the duration of time spent struggling in the FST, while most neuroleptics and anxiolytics do not affect this behavior (Petit-Demouliere et al. 2005; Kara et al. 2018). Chronic administration of antidepressants prior to testing in the FST typically produces more robust effects than are seen acutely (Cryan et al. 2005), mimicking the delayed onset of antidepressant action seen in clinical use. In addition, the duration of immobility in * Christopher L. Kliethermes [email protected] 1
Department of Psychology and Neuroscience, Drake University, 318 Olin Hall, 1344 27th Street, Des Moines, IA 50311, USA
the FST can be increased by exposure to a stressor prior to testing, such as lipopolysaccharide injection or a chronic mild stress protocol (see Dalla et al. 2011; Bogdanova et al. 2013 for reviews), suggesting that changes in FST behavior reflect an underlying stress-like state. This good predictive
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