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.
Johnson
O
O
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Becnel
J
J
Nichols
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CD
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004347:Drug Interactions; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D011985:Receptors, Serotonin; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012919:Social Behavior
C098813:5-HT7 protein, Drosophila; D000662:Amphetamines; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044348:Receptors, Serotonin, 5-HT2; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine