Microdosing ketamine in Drosophila does not block serotonin reuptake, but causes complex behavioral changes mediated by glutamate and serotonin receptors

Microdosing ketamine is a novel depression treatment, but it is not clear how it changes serotonin.Drosophila melanogaster (fruit fly) is a good model to study depressive behaviors. We used fast-scan cyclic voltammetry, video tracking, and feeding assays to measure serotonin and behavior after feeding ketamine and SSRIs to larvae. At microdoses, ketamine did not affect serotonin, which was different from SSRIs. However, higher doses inhibited dSERT. Locomotion and feeding changes were also dose-dependent, and we saw separate effects with NMDA and serotonin receptor drugs in a dSERT mutant. This work facilitates future behavioral and pharmacological testing inDrosophila. AbstractMicrodosing ketamine is a novel antidepressant for treatment-resistant depression. Traditional antidepressants, like selective serotonin reuptake inhibitors (SSRIs), inhibit serotonin reuptake, but it is not clear if ketamine shows a similar mechanism. Here, we tested the effects of feeding ketamine and SSRIs toDrosophila melanogaster larvae, which has a similar serotonin system to mammals and is a good model to track depressive 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 h and found that 1 mM ketamine did not affect serotonin, but increased locomotion and ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research