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.