5-HT regulates transcription independent of BDNF and requires differential activation of either 5-HT1 and/or 5-HT7. A, Average gene expression in hippocampal cells preincubated with the trk receptor antagonist K252a (200 nm) for 30 min before 5-HT treatment (1 μm) followed by real time RT-PCR for a panel of genes. Only one gene, PAI, showed a significantly lower response to 5-HT plus K252a than 5-HT alone. *5-HT plus K252a is significantly different from 5-HT alone (p < 0.05, ANOVA; n = 4). B, C, Average gene expression in hippocampal cells preincubated with 5-HT receptor antagonists for 30 min before BDNF treatment (50 ng/ml) followed by real-time RT-PCR for a panel of genes. B, 5-HT1A antagonist (WAY100635; 10 μm). C, 5-HT7 receptor antagonist (SB269970; 10 μm). No statistical difference was detected between BDNF plus receptor antagonists and BDNF alone for any of the genes (p > 0.05, ANOVA; n = 3). D–F, Average gene expression in neurons preincubated with inhibitors to 5-HT receptor subtypes before 5-CT (1 μm) treatment followed by real-time RT-PCR for the neuropeptides VGF, SP, and NPY. D, 5-HT1A antagonist (WAY100635; 10 μm). E, 5-HT7 antagonist (SB269970; 10 μm). F, Combination of WAY100635 plus SB269970. One group of cells in each experiment was treated with inhibitor alone and showed no significant change in expression relative to vehicle control. *Significant reduction of transcription in the presence of inhibitor plus 5-CT relative to 5-CT alone (p < 0.05, ANOVA; n = 3). All samples were first normalized to GAPDH and then represented as an average ratio of vehicle controls ± SE.