Psychopharmacology (2011) 214:911–921 915 i i * k i k i i i * k i k i Vehicle Ket 10 50 min Ket 10 3 hours Ket 10 24 hours 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 Fig. 1 a–c Relationship be- tween the time of ketamine administration and attentional set-shifting performance in mice. Ketamine (10 mg/kg) was administered 50 min and 3 or 24 h before both sessions. N= 8 mice per treatment condition. 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 at 50 min (the standard ketamine treatment); Newman–Keuls post hoc test A 30 B 25 n iro20 e t i rc 15 o t ls 10 a i rT 5 0 30 i]n25 m [n20 o i itre15 r tco10 e im 5 T 0 n10 o itre 8 i r tco 6 rso 4 r rE 2 0 C 12 SD CD CDR IDS IDSR IDS2 IDSR2 EDS EDSR hydrochloride] (Sequoia, UK) were dissolved in distilled water. Sertindole (Sigma-Aldrich, Germany) was dissolved in a minimum amount of 0.1 M hydrochloric acid and diluted with water. Drugs were administered before each of the two sessions. Therefore, the same animal received drug treatment twice: ketamine at 50 min, 3 h or 24 h (IP), the Ro 25-6981 compound at 30 min (IP), and sertindole at 120 min (PO). The ketamine “24-h” animals received the drug approximately 1 h after the last trial of habituation and approximately 1 h after session 1. All of the compounds were administered in a volume of 10 ml/kg, and the doses were chosen based on in-house data and published literature (Higgins et al. 2005; Rodefer et al. 2008). Statistics The following parameters were measured for each mouse: the number of trials to criterion, the number of errors to criterion, and the time to reach criterion, which was defined as eight correct choices out of ten consecutive trials. Statistical analyses were performed with Statistica 8.0 for Windows. The data from sessions 1 and 2 were calculated separately using repeated measures ANOVAs. Whenever significant interactions between the treatment conditions and the phase of a session were found, the data were analyzed with Newman–Keuls post hoc test; P < 0.05 was deemed significant. Results Modification of the ASST procedure: general remarks The modification of the protocols of Garner et al. (2006) and Papaleo et al. (2008) produced reliable set-shifting in mice because in all replications, the subjects required significantly more trials to reach the criterion during the EDS than during the IDS2 phase of the task. The