Serotonin 5-HT(2) and 5-HT(1A)-like receptors differentially modulate aggressive behaviors in Drosophila melanogaster

Aggressive behavior is widespread throughout the animal kingdom, and is a complex social behavior influenced by both genetics and environment. Animals typically fight over resources that include food, territory, and sexual partners. Of all the neurotransmitters, serotonin (5-HT) has been the most implicated in modulating aggressive behaviors in mammalian systems. In the fruit fly, Drosophila melanogaster, the involvement of 5-HT itself in aggressive behaviors has been recently established, however, the underlying mechanisms have largely remained elusive. Here we describe the influence of different 5-HT receptor subtypes on aggressive behaviors in Drosophila. Drosophila express homologs of three mammalian 5-HT receptors: the 5-HT(1A), 5-HT(2), and 5-HT(7) receptors. Significantly, these receptors mediate important behaviors in mammalian systems ranging from feeding, aggression, and sleep, to cognition. To examine the role of the 5-HT(2)Dro receptor, we utilized the selective 5-HT(2) receptor agonist (R)-1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI), and the 5-HT(2) receptor antagonist, ketanserin. To examine the role of 5-HT(1A)-like receptors we used the 5-HT(1A) receptor agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT), and the 5-HT(1A) receptor antagonist WAY100635. We find that activation of 5-HT(2) receptors with (R)-DOI appears to decrease overall aggression, whereas activation of 5-HT(1A)-like receptors with 8-OH-DPAT increases overall aggression. Furthermore, the different 5-HT receptor circuitries appear to mediate different aspects of aggression: 5-HT(2) receptor manipulation primarily alters lunging and boxing, whereas 5-HT(1A)-like receptor manipulation primarily affects wing threats and fencing. Elucidating the effects of serotonergic systems on aggression in the fly is a significant advancement not only in establishing the fly as a system to study aggression, but as a system relevant to elucidating molecular mechanisms underlying aggression in mammals, including humans.