The Neurotrophic Actions of Serotonin and Dopamine on the Larval Feeding Circuit in Drosophila Are Sexually Dimorphic

The neurotransmitters dopamine (DA) and serotonin (5-HT) exhibit trophic actions on developing neural circuits in addition to their roles as signaling molecules in the nervous system. Improper signaling of these trophic factors during development may underlie the etiology of anxiety, depression, attention-deficit/hyperactivity disorder (ADHD), addiction, obsessive-compulsive disorder, and autism spectrum disorders (ASD). Many neuropsychiatric disorders display sexual dimorphism in their manifestations. Disorders such as schizophrenia, ADHD, and ASD are disproportionately diagnosed in males, whereas anorexia nervosa, addiction, and depression tend to manifest more in females. However, the mechanisms by which this occurs are still unknown. We have previously described the effects of DA and 5-HT on the development on the serotonergic feeding circuit in Drosophila larvae and demonstrated that perturbations in DA and 5-HT levels during central nervous system development affected both the axonal architecture of the serotonergic projections extending from the brain to the foregut and feeding behavior, the functional output of the circuit. Using transgenic lines to reduce synthesis of neuronal DA and 5-HT, we observed differences in feeding behaviors between male and female larvae. In the presence of reduced DA levels, females displayed decreased feeding. Conversely, reduced levels of 5-HT decreased feeding in males to a greater extent than females. The results of these experiments illuminate the sexually dimorphic actions of neurotrophic factors in the development of the central nervous system.