Figure 3

Acute treatment with the mGlu1 receptor PAM, Ro0711401, improves motor performance in symptomatic SCA1 mice. Effect of Ro0711401 on the rotarod in symptomatic SCA1 mice with mild motor impairment (A); values are means ± S.E.M. of 4 mice per group. *p < 0.05 vs. corresponding values at time 0; Two-way ANOVA for repeated measures + Fisher’s LSD: F_(3,21) = 7.621 and F_(1,21) = 10.176 for time and treatment, respectively; and in wild-type littermates (B); data are means ± S.E.M. of 7 mice per group. Lack of effect of JNJ16259685 in SCA1 mice with mild motor impairment and wild-type (C), where data are means ± S.E.M. of 4 mice per group; *p < 0.05 vs. respective values at time 0. Two-way ANOVA for repeated measures + Fisher’s LSD; F_(3,18) = 34.38 and F_(1,18) = 7.24 for time and treatment, respectively. Effect of Ro0711401 in symptomatic SCA1 mice with severe motor impairment (D); values are means ± S.E.M. of 5 mice per group. *p < 0.05 vs. corresponding values at time 0; Two-way ANOVA for repeated measures + Fisher’s LSD; F_(3,12) = 11.177 and F_(4,39) = 9.982 for time and time x treatment, respectively. Paw print test in SCA1 mice with severe motor impairment and wild-type acutely treated with Ro0711401 (E). Data were quantified by calculating the coefficient of variation of 5 consecutive strides with the left paw of each mouse. Values are means ± S.E.M. of 9 mice. *p < 0.05 (One-Way ANOVA plus Fisher’s PLSD) vs. SCA1 mice before the treatment. Representative traces were carried out 5 min prior and 60 min after drug injection. Motor performance on the rotarod of mGlu1-deficient crv4 mice and wild-type mice 1 hour following s.c. injection of vehicle or Ro0711401 (F). Values are means + S.E.M. of 4 mice per group.