Figure 2

Serotonergic expression of p38α MAPK is required for acute interleukin (IL)-1β-induced SERT activation. (a) High-performance liquid chromatography (HPLC) analysis of 5-hydroxytryptamine (5-HT) levels in the midbrain (MB), forebrain (FB), hippocampus (Hip) and striatum (Str) from male p38α^5HT+ and p38α^5HT− mice. Two-way analysis of variance (ANOVA) indicates significant region (F_3,67=71.75, P<0.0001) and genotype (F_{1, 67},=4.12, P=0.001) effects and a nonsignificant interaction (F_3,67=0.53, P=0.67). N for all regions=10 for p38α^5HT+, N=8 for p38α^5HT−. (b) Basal firing rate of dorsal raphe 5-HT neurons as assessed by cell-attached recordings of serotonergic neurons in acute midbrain slices from p38α^5HT+ and p38α^5HT− mice, N=10 neurons from three p38α^5HT+ mice, N=15 neurons from three p38α^5HT− mice, with data derived from two to three slices per animal. Student’s two-tailed t-test reveals no significant genotype effect. (c) SERT protein expression in MB and FB of p38α^5HT+ and p38α^5HT− mice assessed by western blotting. Two-way ANOVA indicates no significant region or genotype effects. N=7 for all groups. (d) Transport of [³H]-5HT (50 nM) in MB synaptosomes of p38α^5HT+ and p38α^5HT− mice following treatment with IL-1β (10 ng ml⁻¹), compared with vehicle. Two-way ANOVA indicates significant drug × genotype interaction (F_{1, 20}=6.68, P=0.02), drug (F_{1, 20}=5.62, P=0.02), and genotype (F_{1, 20}=6.68, P=0.02). Bonferroni post hoc shows a significant effect of IL-1β in lipopolysaccharide (LPS)-treated p38α^5HT+, but not p38α^5HT− mice, compared with vehicle control counterparts. *P<0.05; **P<0.01, N=6 for all groups.