Serotonin 5‐HT1A‐like, 5‐HT2, and 5‐HT7 Receptors Modulate Learning and Memory in Drosophila

Serotonin is a neurotransmitter involved in many behaviors in mammals including regulation of mood, appetite, sleep, memory, aggression, and sexual behavior. In the fly, serotonin has also been demonstrated to be involved in many of these same complex behaviors. The effects of serotonin are primarily mediated through interactions with G‐protein coupled receptors to initiate multiple signal transduction pathways. Drosophila expresses orthologs of four mammalian 5‐HT receptor subtypes: 5‐HT 1A Dro, 5‐HT 1B Dro, 5‐HT 2 Dro, and 5‐HT 7 Dro. Here, we present data demonstrating involvement of all three serotonin receptor families in olfactory learning and memory in the fly. We probed the involvement of the 5‐HT 1A ‐like, 5‐HT 2 , and 5‐HT 7 receptors in short‐term memory in the fly. The 5‐HT 1A receptor agonist U92106A and the 5‐HT 1A receptor antagonist WAY100635 reduced performance indices in a dose‐dependent manner. The 5‐HT 2 receptor agonist DOI, and the 5‐HT 2 receptor antagonist ketanserin also abated performance indices in a dose‐dependent manner (IC 50 value for DOI = 0.21 mM). A putative 5‐HT 7 receptor antagonist SB 269970, also diminished performance levels. Since both agonists and antagonists for a given receptor inhibit performance, a homeostasis likely exists at each receptor, and perturbation of homeostasis disrupts this behavior. Research support: NIMH grants 5R21MH078454‐02 and 3R21MH078454‐01A1S1