Mutation of theDrosophilaserotonin transporter dSERT disrupts courtship and feeding and increases both daytime and nighttime sleep

Abstract

AbstractThe Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organismDrosophila melanogaster, we developed new loss of function mutations inDrosophila SERT(dSERT).Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generateddSERTmutants show an increase in total sleep and altered sleep architecture. Differences in daytime vs. nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep.dSERTmutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs. Starvation did not overcome the sleep drive in the mutants. Additionally in males, but not femaledSERTmutants, the drive to mate also failed to overcome sleep drive.dSERTmay be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors.Author SummaryMany medications used to treat depression and anxiety act by changing serotonin levels in the brain. Fruit flies also use serotonin and can be used as a model to study the brain. We have made a fly mutant for the serotonin transporter (SERT), which is the target of antidepressants in humans. The mutants sleep more, eat less, and have a decreased sex drive. These flies can be used to study the neuronal pathways by which serotonin regulates sleep, eating and sexual behaviors and may help us to understand the behavioral effects of antidepressants.