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. 2018 Jan 22;5(3):297–314. doi: 10.1002/acn3.527

Figure 4.

Figure 4

Chlorzoxazone and baclofen, but not SKA‐31 and baclofen, sustains improvement in motor dysfunction in ATXN1[82Q] mice. (A) Drug administration and behavioral testing paradigm. (B) Correlated brain and plasma levels of SKA‐31 are seen after administration through drinking water (R 2 = 0.1337). (C) Correlated brain and plasma levels of chlorzoxazone are seen after administration through drinking water (R 2 = 0.8904). (D) Correlated brain and plasma levels of baclofen are present after administration through drinking water (R 2 = 0.8591). (E) After 1 week of treatment, SKA‐31 + baclofen improves motor performance in ATXN1[82Q] mice (F(2, 113) = 15.76, P < 0.0001) (Wild‐type + Vehicle vs. ATXN1[82Q] + Vehicle P < 0.0001; Wild‐type + Vehicle vs. ATXN1[82Q] + SKA‐31 + Baclofen P < 0.0001; ATXN1[82Q] + Vehicle vs. ATXN1[82Q] + SKA‐31 + Baclofen P = 0.004). (F) After 1 week of treatment, chlorzoxazone + baclofen improves motor performance in ATXN1[82Q] mice (F(3, 156) = 42.23, P < 0.0001) (Wild‐type + Vehicle vs. Wild‐type + Chlorzoxazone + Baclofen P = 0.9726; Wild‐type + Vehicle vs. ATXN1[82Q] + Vehicle P < 0.0001; Wild‐type + Vehicle vs. ATXN1[82Q] + Chlorzoxazone + Baclofen P < 0.0001; Wild‐type + Chlorzoxazone + Baclofen vs. ATXN1[82Q] + Vehicle P < 0.0001; Wild‐type + Chlorzoxazone + Baclofen vs. ATXN1[82Q] + Chlorzoxazone + Baclofen P < 0.0001; ATXN1[82Q] + Vehicle vs. ATXN1[82Q] + Chlorzoxazone + Baclofen P = 0.0036). (G) After 10 weeks of treatment, mice treated with SKA‐31+ baclofen show worsened motor performance compared with vehicle‐treated controls (F(2, 109) = 36.73, P < 0.0001) (Wild‐type vs. ATXN1[82Q] + Vehicle P = 0.0005; Wild‐type vs. ATXN1[82Q] + SKA‐31 + Baclofen P < 0.0001; ATXN1[82Q] + Vehicle vs. ATXN1[82Q] + SKA‐31 + Baclofen P = 0.0408). (H) After 10 weeks of treatment, ATXN1[82Q] mice treated with chlorzoxazone + baclofen display sustained improvement in motor performance compared with vehicle‐treated controls (F(3, 144) = 29.43, P < 0.0001) (Wild‐type + Vehicle vs. Wild‐type + Chlorzoxazone + Baclofen P = 0.0292; Wild‐type + Vehicle vs. ATXN1[82Q] + Vehicle P < 0.0001; Wild‐type + Vehicle vs. ATXN1[82Q] + Chlorzoxazone + Baclofen P = 0.0097; Wild‐type + Chlorzoxazone + Baclofen vs. ATXN1[82Q] + Vehicle P < 0.0001; Wild‐type + Chlorzoxazone + Baclofen vs. ATXN1[82Q] + Chlorzoxazone + Baclofen P < 0.0001; ATXN1[82Q] + Vehicle vs. ATXN1[82Q] + Chlorzoxazone + Baclofen P = 0.0029). *P < 0.05, ** P < 0.01, two‐way ANOVA with Holm–Sidak posttest. CHZ, chlorzoxazone.