Fig. 3. SEP-856 demonstrates antipsychotic- and antidepressant-like activity without inducing catalepsy. (A) Oral SEP-856 administration dose-dependently reduced PCP-induced hyperactivity in C57BL/6J mice (one-way ANOVA + Tukey’s post hoc test, *P < 0.05 vs. Veh/PCP, #P < 0.05 vs. Veh/Veh). Clozapine and PCP were dosed at 1 and 5 mg/kg i.p., respectively. (B) PPI measured in C57BL/6J mice was significantly increased by haloperidol (i.p.) and SEP-856 at 3, 10, and 30 mg/kg (p.o.) compared with their respective vehicle controls (10% DMSO for haloperidol and 20% cyclodextrin for SEP-856; one-way ANOVA + Tukey’s post hoc test, *#P < 0.05). (C) Social interaction deficits induced by subchronic PCP treatment (2.5 mg/kg, s.c., twice daily for 5 days) in Sprague-Dawley rats were significantly attenuated by acute clozapine (2.5 mg/kg, i.p.) and SEP-856 (p.o.) treatment at all doses tested (one-way ANOVA + Tukey’s post hoc test, *P < 0.05 vs. PCP/Veh, #P < 0.05 vs. Veh/Veh). (D) Acute sertraline (20 mg/kg, i.p.) and 1, 3, and 10 mg/kg SEP-856 (p.o.) dosing reduced immobility time in the FST in Balb/CJ mice compared with vehicle controls (one-way ANOVA + Tukey’s post hoc test, *P < 0.05 vs. Veh). (E) In contrast to haloperidol (i.p.), acute SEP-856 (p.o.) treatment did not induce catalepsy in the mouse (C57BL/6J) bar test, as seen by the lack of increase in time spent holding the bar compared with vehicle (two-way ANOVA + Tukey’s post hoc, *P < 0.05 vs. Veh). CLZ, clozapine; SRT, sertraline. N = 8–12/group. Data are shown as mean ± S.E.M.