Fig. 1.

Effect of chronic antidepressant treatment on dopamine D1 receptor expression and signaling in the dentate gyrus. a D1 receptor protein (DRD1) expression in the prefrontal cortex (PFC), dorsal striatum (Str), dentate gyrus (DG), and spinal cord (SC) in fluoxetine (FLX; 15 mg/kg/day for 14 days) or placebo (PL) pellet-treated mice. 60 μg (prefrontal cortex, dentate gyrus, and spinal cord) or 6 μg (striatum) of samples were analyzed. Typical immunoblots are shown with quantitation. DRD1 expression is normalized with β-actin. Data represent mean ± SEM. *p < 0.05 vs. the placebo group; paired Student’s t test. b Drd1 mRNA expression in various brain regions in fluoxetine or placebo pellet-treated mice. NAc nucleus accumbens. Data represent mean ± SEM. *p < 0.05 vs. the placebo group; Student’s t test. c Time course of fluoxetine effects on Drd1 mRNA expression in the dentate gyrus. Data represent mean ± SEM. **p < 0.01, ***p < 0.001 vs. the placebo group; two-way ANOVA and Bonferroni post hoc test. d mRNA expression of Drd1, calbindin-D28K (Calb1) and Tdo2 in the dentate gyrus in imipramine (IMI; 10 mg/kg/day for 14 days) or placebo (PL) pellet-treated mice. Data represent mean ± SEM. *p < 0.05, **p < 0.01 vs. the placebo group; Student’s t test. Data in (a−d) are normalized and represented as fold changes by fluoxetine or imipramine. e Immunofluorescence signal of a nuclear dye DraQ5, [Drd1]-EGFP and Calbindin-D28K in the dentate gyrus from [Drd1]-EGFP mice treated with the fluoxetine or placebo pellet. ML molecular layer, GC granule cell layer, H hilus. Scale bars, 100 µm. f Effects of a D1 receptor agonist, (±)-SKF81297 (1 and 10 µM), on PKA-mediated DARPP-32 phosphorylation in slices of the dentate gyrus from mice treated with the fluoxetine or placebo pellet. Typical immunoblots for detection of phospho-Thr34 and total DARPP-32 are shown with quantitation. Data represent mean ± SEM. **p < 0.01 vs. the placebo group; two-way ANOVA and Bonferroni post hoc test. g Effect of D1 receptor blockade with a specific antagonist, SCH23390 (SCH; 0.1 mg/kg/day i.p. for 14 days), on fluoxetine-induced changes in the gene expression of Drd1, Calb1 and Drd5 in the dentate gyrus. Data represent mean ± SEM. **p < 0.01, ***p < 0.001 vs. the fluoxetine (−)/SCH23390 (−) group; ⁺⁺p < 0.01, ⁺⁺⁺p < 0.001 vs. the fluoxetine (+)/SCH23390 (−) group; one-way ANOVA and Newman−Keuls post hoc test. The number of mice is indicated in parentheses under each experimental condition