Figure 5: Effect of local hippocampal administration of H₃R/H₄R ligands on the clearance of exogenously supplied 5-HT.

in-vivo 5-HT clearance in the hippocampus of anesthetized rats was monitored by chronoamperometry as described in the Methods. (A) in-vivo effect of H₃R/H₄R agonist immepip on 5-HT clearance. Once reproducible 5-HT signals were obtained, immepip (20 pmol) was pressure ejected into the hippocampus, and 2 min later followed with 5-HT. Shown are representative oxidation currents (using in vitro calibration factor, current was converted to a micromolar value) produced by pressure-ejection of 5-HT into hippocampus either before (grey trace) or after (black trace) locally applying immepip. Traces are overlaid for ease of comparison. (C) 5-HT clearance T₈₀ (time to clear 5-HT by 80%) as a function of time elapsed after local application of immepip. Data are expressed as percentage change from pre-drug/vehicle baseline. ***p< 0.001, *p< 0.05 compared with vehicle baseline (Two-Way ANOVA with Bonferroni multiple comparison tests). (E) The maximum effect of immepip on T80 2 min post-application. (***p< 0.0003, Two-tailed Student’s t-test, n is shown within the bars). (B) in vivo effect of H₃R/ H₃R inverse agonist thioperamide on 5-HT clearance. Following reproducible 5-HT signals, thioperamide (20 pmol) was pressure ejected into hippocampus, 2 min later followed with 5-HT. Shown are representative oxidation currents produced by pressure-ejection of 5-HT in hippocampus either before (grey trace) or after (black trace) locally applying thioperamide. (D) 5-HT clearance T₈₀ (time to clear 5-HT by 80%) as a function of time elapsed after local application of thioperamide. Data are expressed as percentage change from pre-drug/vehicle baseline. There was a main effect of treatment (***p<0.0002 (Two-Way ANOVA with Bonferroni multiple comparison tests). (F) The maximum effect of thioperamide on T80, 5 min post-application. (*p < 0.01, Two-tailed Student’s t-test, n is shown within the bars). Thio: thioperamide.