Fig. 3.

Visible platform training and spatial learning in the problem-solving task of the water maze, following either (a–d) MTC or (e–h) LMTX treatment. (a) Path length (including trial 1 of the first day of training) and (b) swim speed of the MTC cohorts recorded during 4 days of cued training. Although there was no difference between L1 and WT mice in path length, L1 mice swam significantly faster; however, there was no effect of MTC. Representative sample swim traces for MTC cohorts are shown in (c). Differences in the mean number of trials required to reach criterion in three problems (d) for the different MTC cohorts of L1 suggests deficits in these mice. Compared with vehicle-treated WT mice, L1 mice required more trials to attain criterion (asterisks), and this was reversed by MTC at 45 mg/kg. (e) Path length and (f) swim speed of LMTX cohorts recorded during cued training. Although there were small differences between L1 and WT in path length, the cohorts did not differ in trial 1 or in the final trials on day 4. Again, L1 mice swam consistently faster, but there was no effect of LMTX. (g) Representative sample swim traces of LMTX cohorts. (h) Results of the mean trial number required to reach criterion in three problems for the different LMTX cohorts confirm an impairment in L1 mice treated with vehicle (asterisks). Both 15 and 45 mg/kg LMTX reversed these deficits. The 45 mg/kg doses are equivalent to 35.1 mg MT/kg and 26.7 mg MT/kg for MTC and, in this case, LMTM, respectively. Values are expressed as mean±SE. *P<0.05; **P<0.01; ****P<0.0001. L1, Line 1; LMTX, leucomethylthioninium salt; MT, methylthioninium; MTC, methylthioninium chloride; WT, wild type.