SD CD CDR IDS IDSR IDS2 IDSR2 EDS EDSR SD CD CDR IDS IDSR IDS2 IDSR2 EDS EDSR session 1 session 2 session 1 session 2 Psychopharmacology (2011) 214:911–921 Vehicle Ket 10 50 min Ket 20 50 min session 1 session 2 i i i i * i * i * k i * k i * k i * 916 Fig. 2 a–c Dose-dependent effects of ketamine on the attentional set-shifting task in mice. Ketamine (10 or 20 mg/ kg) was administered 50 min before both sessions. N=8–9 mice per treatment. Data are presented as the mean ± SEM. Symbols: *P<0.05 vs. vehicle, iP<0.05 vs. IDS2 phase, kP<0.05 vs. ketamine 10 mg/kg group; Newman–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 interaction factor between treatment conditions and the session phase for all of the experiments’ session 1 measures, including trials, errors, and time to criterion, yielded insignificant results. Time-related effects of ketamine on ASST performance As assessed by the interaction factors between treatment condition and the phase of a given session, ketamine (10 mg/kg, 3 or 24 h before the test) changed neither the number of trials and errors nor the time to reach the criterion at any of the discrimination phases (Fig. 1a–c). In contrast, when administered 50 min before testing, ket- amine significantly increased the number of trials (F(9, 84)= 2.72, P< 0.01; Fig. 1a) and errors (F(9, 84)= 2.86, P< 0.01; Fig. 1c) to criterion during the EDS phase. Although the time to criterion in this group was increased (Fig. 1b), the interaction (treatment × phase) for session 2 yielded insignificant results. Dose-related effects of ketamine on ASST performance Ketamine (10 and 20 mg/kg, administered 50 min before the test) dose-dependently, significantly, and specifically increased the number of trials (F(6, 66)=17.49, P<0.001; Fig. 2a), errors (F(6, 66)=8.22, P<0.001; Fig. 2b), and the time to criterion (F(6, 66)=9.04, P<0.001; Fig. 2c) during the EDS phase. In all three measures, the effects of 20 mg/kg ketamine were significantly stronger than the effects of 10 mg/kg. Effects of sertindole on ketamine-induced deficits in the ASST Similar to the two earlier experiments, 10 mg/kg of ketamine administered 50 min before the sessions increased both the number of trials (F(3, 84) = 2.62, P < 0.05; Fig. 3a) and errors (F(3, 84)= 2.67, P < 0.05; Fig. 3c) to criterion during the EDS phase. Sertindole + ketamine treatment decreased these measures to the levels of the control group, and they were