Abstract: AimTo determine whether serotonin, a major neurotransmitter in brain, can modulate the production of secretory β-amyloid protein precursor (sAPP) by activation of serotonin 5-HT_2C receptor. Methods The hippocampal slices of rats were incubated with various concentrations of serotonin, M-110, or L-107. sAPP released into the incubation medium were assayed by Western blot analysis assay with monoclonal antibody 22C11 for 2 h. ResultsVarious concentrations of serotonin (1.0×10^-2-1.0×10³ μmol·L^-1), M-110, a serotonin 5-HT_2C agonist (1.5×10^-6-1.5×10³ μmol·L^-1), showed positive effect on the production of sAPP while L-107, a serotonin 5-HT_2C antagonist (1.0×10-9-1.0×10³ μmol·L^-1), showed negative effect on the production of sAPP over controls. ConclusionSerotonin modulates production of secretory amyloid β-protein precursor through serotonin 5-HT_2C receptor in incubated rat hippocampal slices.