Microdosing ketamine in Drosophila does not inhibit SERT like SSRIs, but causes behavioral changes mediated by glutamate and serotonin receptors
bioRxiv Preprint Server November 7, 2023 Kelly E. Dunham, Kani H. Khaled, Leah Weizman et al. preprint
Ketamine, recently FDA-approved for treatment-resistant depression, does not work like traditional SSRIs at low doses. In fruit fly larvae, which have a serotonin system similar to mammals, 1 mM ketamine did not affect serotonin reuptake but increased locomotion and feeding. Low doses of SSRIs (escitalopram and fluoxetine) inhibited serotonin reuptake and also increased feeding and locomotion. At a high dose (100 mM), ketamine inhibited serotonin reuptake and increased serotonin concentrations but decreased locomotion and feeding due to anesthetic effects. Low doses of other NMDA receptor antagonists increased feeding, while serotonin receptor agonists increased locomotion, suggesting ketamine affects behavior through multiple mechanisms, not by blocking serotonin reuptake like SSRIs.