Serotonin reuptake inhibitors used for the treatment of depression act by increasing serotonin levels at the synaptic cleft and thereby activating 5-HT(1A) serotonin receptors. However, the effect of increased levels of serotonin on postsynaptic 5-HT(1A) receptor density is unknown. The purpose of this study was to investigate, in a culture model, how postsynaptic 5-HT(1A) receptors are influenced by serotonin. Different concentrations of serotonin (0.5, 1, 10, 50 and 100 microM) were added to organotypic hippocampal cultures and incubated for 1 week. The cultures were immunostained for the 5-HT(1A) receptor and the staining analyzed densitometrically. 5-HT(1A) levels decreased with increasing serotonin concentrations, being significant at 10, 50 and 100 microM. These results indicate that at increasing serotonin levels the density of postsynaptic 5-HT(1A) receptors is down-regulated.