5-HT2 receptors in Drosophila are expressed in the brain and modulate aspects of circadian behaviors.
Dysregulation of 5-HT(2) receptor function has been strongly implicated in many neuropsychiatric disorders, including schizophrenia. At present, the molecular mechanisms linking 5-HT(2) receptor activation to behaviors is not well understood. In efforts to elucidate these processes, the fruit fly, Drosophila melanogaster, is proposed to serve as a powerful genetically tractable model organism to study 5-HT(2) receptor function. Data are presented here on the expression of the fly ortholog of the mammalian 5-HT(2) receptor, 5-HT(2)Dro, in the larval and adult brain of the fly, and on the involvement of these circuits in certain circadian behaviors. In the adult brain, 5-HT(2)Dro is expressed in the protocerebrum and ellipsoid body, areas believed to participate in higher order behaviors including learning, locomotion, and sensory perception. In the third instar larva, 5-HT(2)Dro receptor expression is detected in a specific pattern that markedly changes from early to late third instar. To probe the function of this receptor we have examined the effects of the 5-HT(2) receptor-specific agonist DOI in wild type and 5-HT(2)Dro hypomorphic flies on circadian behaviors. DOI was found to increase early day activity, eliminate anticipatory behavior, and reduce viability. The effects of DOI were significantly diminished in a 5-HT(2)Dro hypomorphic strain. Identifying the 5-HT(2)Dro receptor circuitry and behaviors they mediate are significant steps towards developing this model system to study conserved molecular mechanisms underlying behaviors mediated by 5-HT(2) receptors in mammalian systems.
Nichols
Charles D
CD
Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, Louisiana, USA. cnich1@lsuhsc.edu
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D029721:Drosophila Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D015870:Gene Expression; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D029721:Drosophila Proteins; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists