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Microdosing ketamine in Drosophila does not inhibit SERT like SSRIs, but causes behavioral changes mediated by glutamate and serotonin receptors by Kelly E. Dunham; Kani H. Khaled; Leah Weizman; B. Jill Venton is a scholarly article available to read on EtoBox.

What is Microdosing ketamine in Drosophila does not inhibit SERT like SSRIs, but causes behavioral changes mediated by glutamate and serotonin receptors about?

## Abstract Recently, the FDA approved microdosing ketamine for treatment resistant depression. Traditional antidepressants, like serotonin selective reuptake inhibitors (SSRIs), block serotonin reuptake, but it is not clear if ketamine blocks serotonin reuptake. Here, we tested the effects of feeding ketamine and SSRIs to__Drosophila melanogaster__larvae, which has a similar serotonin system to mammals, and is a good model to track depression behaviors, such as locomotion and feeding. Fast-scan cyclic voltammetry (FSCV) was used to measure optogenetically-stimulated serotonin changes, and locomotion tracking software and blue dye feeding to monitor behavior. We fed larvae various doses (1-100 mM) of antidepressants for 24 hours and found that 1 mM ketamine did not affect serotonin, but increased locomotion and feeding. Low doses (≤ 10 mM) of escitalopram and fluoxetine inhibited dSERT and also increased feeding and locomotion behaviors. At 100 mM, ketamine inhibited dSERT and increased serotonin concentrations, but decreased locomotion and feeding due to its anesthetic properties. Since microdosing ketamine causes behavioral effects, we also investigated behavior changes with low

Author

Kelly E. Dunham; Kani H. Khaled; Leah Weizman; B. Jill Venton

Publisher

Cold Spring Harbor Laboratory

Published

2023