(A) Effect of immepip on SERT activity in different brain regions. Synaptosomes isolated from the hippocampus, striatum, midbrain, brainstem, and cortex were pretreated with the vehicle or immepip (500 nM) for 15 min at 37°C. SERT specific 5-HT uptake was measured as described in the Methods and Figure 1. **P< 0.003, *P< 0.03 compared to corresponding vehicle control, ns: nonsignificant (unpaired two-tailed Student’s t-test). (B) Effect of immepip on SERT-mediated [3H]5-HT efflux. Hippocampal synaptosomes were preloaded with [3H]5-HT and fluoxetine-sensitive [3H]5-HT efflux was measured as described in the Methods. [3H]5-HT-preloaded synaptosomes were treated with vehicle or D-fenfluramine (2 μM) or immepip (500 nM) or D-fenfluramine (2 μM) + immepip (500 nM) for 30 min at 37°C. ****P< 0.0001 compared with vehicle control, ^^^^P< 0.0001 compared with immepip, ns: nonsignificant (One-Way ANOVA with Bonferroni multiple comparison tests). HC: hippocampus, St: striatum, MB: midbrain, BS: brain stem, Ctx: cortex, V: vehicle, Fen: D-fenfluramine, Imm: immepip.