The 5‐HT₇Dro Serotonin Receptor: Expression in the CNS and Function

Abstract

Serotonin (5‐HT) influences behaviors that include circadian, sleep, appetite, aggression, locomotion, perception, and sexual behavior. The effects of 5‐HT are mediated through G‐protein coupled receptors, which initiate multiple effector pathways. Disregulation of 5‐HT signaling in humans has been implicated in neuropsychiatric disorders including depression, anxiety disorders, anorexia and schizophrenia. The fruit fly, Drosophila melanogaster, expresses orthologs of three mammalian 5‐HT receptor subtypes: 5‐HT1A, 5‐HT2, and 5‐HT7. The 5‐HT7Dro receptor is orthologous to the mammalian 5‐HT7 receptor and activates adenylate cyclase through Gαs. We show that in fly 3rd instar larvae brain, 5‐HT7Dro expression is observed in discreet populations of neurons in the hemispheres as well as in neurons of the ventral ganglia. In adult brains, 5‐HT7Dro is highly expressed in neurons that innervate the ellipsoid body, a region believed to be involved in higher order behaviors. 5‐HT7Dro neurons also cluster with PDF‐positive circadian pacemaker neurons. Pharmacological studies using the 5‐HT1A/7 receptor agonist 8‐OH‐DPAT with the 5‐HT1A receptor antagonist WAY100635 eliminated circadian activity. These results suggest that 5‐HT7Dro may modulate circadian activity in the fly. Further studies to determine the role of 5‐HT7Dro in additional behaviors are ongoing. Supported by NIMH 1R21MH078454