Fig. 5. Inhibition of TrkB in the dorsal striatum blocked the therapeutic effects of 7,8-DHF. (A) Experimental designs. In Exp.#1, CON-siRNA or TrkB-siRNA was injected in the dorsal striatum (AP, +1.0; ML, ±1.5; DV, −3.6 mm) of normally raised WT mice, and the mice were sacrificed on day 3. In Exp.#2, CON-siRNA or TrkB-siRNA was injected in the dorsal striatum of normally raised WT mice or ELS-exposed D2+/− mice, followed by 7,8-DHF injection (i.p., 10 mg/kg/day) and subsequent behavioral tests. (B, C) Western blots showing expression levels of TrkB, p-AKT, AKT, p-ERK1/2, ERK1/2, and β-Actin in the dorsal striatum injected with TrkB-siRNA or CON-siRNA (B). Samples were collected 2 days after siRNA injection. Quantification of Western blots (C). n= 4 animals, each, 3–4 repeats (TrkB: p=0.0002; p-AKT/AKT: p=0.0367; p-ERK/ERK: p=0.0014). (D~F) The amount of time spent in each chamber in the three-chamber test (D), social interaction time in the home-cage social interaction test (E), and grooming time (F) of normally raised WT mice and ELS-exposed D2+/− mice injected with TrkB-siRNA or CON-siRNA in the dorsal striatum and treated with vehicle or 7,8-DHF as indicated. n=5~6 animals (three-chamber test: WT, CON+siCON+Veh: p=0.0017; WT, CON+siTrkB+Veh; p=0.0015; D2+/−, ELS+siCON+Veh: p=0.5463, D2+/−, ELS+siCON+DHF: p=0.0025, D2+/−, ELS+siTrkB+DHF: p=0.9304; Grooming, WT, CON+siCON+Veh vs. WT, CON+siTrkB+Veh: p=0.9081; D2+/−, F(2, 14)=0.2332, p=0.7950). Data are presented as mean±SEM. * and ** denote differences between the indicated groups at p<0.05 and p<0.01, respectively (Student's t-test or one-way ANOVA and Holm-Sidak post hoc test).
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