Fig. 2.

Effect of GRN-529 on repetitive self-grooming in BTBR and stereotyped jumping in C58 mice. Cumulative time spent self-grooming by BTBR and B6 mice was scored over a 10-min session in a clean, closed, empty cage after a 10-min acclimation period. Observations of stereotyped jumping behavior in C58 mice were quantified for a period of 10 min. GRN-529 was tested in two independent laboratory environments across three cohorts. (A) B6 mice did not display any significant differences in the amount of time spent self-grooming after treatment with vehicle (10% Tween 80/saline) or GRN-529 at doses of 0.3, 1.0, or 3.0 mg/kg intraperitoneally (n = 8 to 10 per dose, cohort 1, tested at NIMH, *P < 0.05 versus vehicle). (B) BTBR displayed significant reductions in their innately high levels of repetitive self-grooming after treatment with GRN-529 at doses of 1.0 and 3.0 mg/kg (n = 11 to 14 per dose, cohort 1, tested at NIMH, *P < 0.05 versus vehicle). (C) B6 mice displayed significant reductions in the amount of time spent self-grooming after treatment with GRN-529 at doses of 1.0 and 3.0 mg/kg compared to vehicle (cohort 2, tested at Pfizer). (D) BTBR again displayed significant reductions in high levels of repetitive self-grooming after treatment with GRN-529 at doses of 1.0 and 3.0 mg/kg intraperitoneally (n = 17 to 25 per dose for each strain, cohort 2, tested at Pfizer, *P < 0.05 versus vehicle). (E) Stereotyped vertical jumping in C58 mice was significantly reduced after GRN-529 administration at doses of 0.3, 1.0, and 3.0 mg/kg intraperitoneally versus vehicle (*P < 0.05, tested at Pfizer). (F) No adverse or sedating effects on the general activity of C58 mice were observed during open field locomotion (P > 0.05, tested at Pfizer).