TrkB-Fc blocks the TrkB receptor agonistic activity of 7,8-DHF. Primary neurons (DIV 13) were preincubated with gradually increasing doses of TrkB-Fc for 15 min, followed by addition of BDNF (100 ng/ml) or 7,8-DHF (100 nm) for another 15 min. A, the cell lysates were analyzed by immunoblotting (IB) with various indicated antibodies. BDNF or 7,8-DHF-triggered TrkB phosphorylation and its downstream p-Akt and p-MAPK signals were inhibited progressively by TrkB-fc recombinant proteins. M.W., molecular weight; Ct, control. B, quantitative analysis of p-TrkB/Total TrkB from independent experiments. *, p < 0.05 versus control; #, p < 0.005 versus BDNF or 7,8-DHF treatment only; one-way analysis of variance, Tukey's multiple comparison test, n = 2.