Vehicle Ketamine 10 Sertindole 2.5 Sertindole 2.5 + Ketamine 10 session 1 session 2 SD CD CDR IDS IDSR IDS2 IDSR2 EDS EDSR session 1 session 2 session 1 session 2 SD CD CDR IDS IDSR IDS2 IDSR2 EDS EDSR Psychopharmacology (2011) 214:911–921 Fig. 3 Effects of sertindole on ketamine-induced deficits in the attentional set-shifting task in mice. Sertindole (2.5 mg/kg) and ketamine (10 mg/kg) were administered 2 h and 50 min before both sessions, respec- tively (N=7–9 mice per treat- ment). Data are presented as the mean ± SEM. Symbols: * P<0.05 vs. vehicle, iP<0.05 vs. IDS2 phase, kP<0.05 vs. ket- amine 10 mg/kg group; New- man–Keuls post hoc test A 30 25 iron20 e itrc 15 o lts 10 a irT 5 0 ] 25 n i [m20 n iro15 e t irc 10 o te 5 m iT 0 B 30 C 12 10 n iro 8 e t irc 6 o trs 4 o rrE 2 0 SD CD CDR IDS IDSR IDS2 IDSR2 EDS EDSR significantly lower compared to the ketamine alone treat- ment. Sertindole (2.5 mg/kg) did not change the number of trials or errors to criterion during the EDS phase compared with the vehicle-treated and sertindole + ketamine-treated groups (Fig. 3a, c). In this set of data, the time to criterion measure (Fig. 3b) was not affected by any of the treatments. Dose-related effects of Ro 25-6981 on ASST performance Ro 25-6981, administered 30 min before both sessions at 10 mg/kg, but not at 3 mg/kg, significantly and specifically facilitated performance during the EDS phase. The higher dose decreased the number of trials (F(6, 63)=4.97, P<0.001; Fig. 4a) and errors (F(6, 63)=4.27, P<0.01; Fig. 4c) to criterion compared to the vehicle-treated group and compared to the group treated with the lower dose. The time to criterion measure (Fig. 4b) was not affected by these treatments. Effects of Ro 25-6981 on ketamine-induced deficits in the ASST Ketamine (10 mg/kg) increased the number of trials to criterion during the EDS phase, but the Ro 25-6981 treatment alone (10 mg/kg) decreased this measure com- pared to the vehicle-treated group (F(3, 84) = 8.72, P < 0.001; Fig. 5a), confirming our earlier findings. The administration of Ro 25-6981 to ketamine-pretreated mice decreased the number of trials to criterion during the EDS phase compared to the vehicle- and ketamine-treated groups (Fig. 5a). A similar pattern of effects was observed for the errors to criterion measure; however, this statistical analysis yielded insignificant results (P= 0.10; Fig. 5c). Ketamine (10 mg/kg) prolonged the time to criterion during the EDS phase (see also Fig. 2), and the ketamine + Ro 25-6981 treatment decreased this measure compared to the ketamine alone group (F(3, 84) = 4.09, P < 0.01; Fig. 5b). Similar to the earlier experiment, the Ro 25-6981 treatment shortened the time to criterion compared to the vehicle-treated group, but statistical analysis yielded insignificant differences. Discussion The present study demonstrated a procedure of attentional set-shifting in mice capable of revealing a deficit during the EDS phase, which was further impaired by ketamine i i * k k i i i i * k ki i 917