5-HT2 receptors in Drosophila are expressed in the brain and modulate aspects of circadian behaviors

Dysregulation of 5-HT2 receptor function has been strongly implicated in many neuropsychiatric disorders, including schizophrenia. At present, the molecular mechanisms linking 5-HT2 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-HT2 receptor function. Data are presented here on the expression of the fly ortholog of the mammalian 5-HT2 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-HT2 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 5HT(2) receptors in mammalian systems. (C) 2007 Wiley Periodicals, Inc.