920 accuracy, and traxoprodil improves accuracy and increases response speed in the DMTP task (Higgins et al. 2005). These authors conclude that selective NR2B NMDA antagonists promote impulsive-type responding that—under certain test conditions, such as a higher event rate of stimulus presentation—results in an improvement of task performance. Somewhat similar results have been reported by Gilmour et al. (2009), who show that NR2B-specific antagonists increase instrumental output in a series of variable interval schedules of reinforcement in an operant task. Our data appear to confirm these findings because the treatment with Ro 25-6981 not only reduced the number of trials to criterion (Fig. 4a) but also reduced, albeit insignificantly, the time required to complete the EDS phase of the set-shifting task (Figs. 4b and 5b). The present data cannot offer a convincing explanation of the mechanism for the pro-cognitive action of Ro 25- 6981. The ASST does not allow for the measurement of all of the parameters that are typically recorded in 5-CSRT and is a relatively simple procedure with a remarkably lower workload. Nonetheless, we may speculate that the Ro 25- 6981-induced reduction in the number of trials to criterion and in the time to complete the EDS phase resembles a similar improvement in performance (response speed and accuracy) as the improvements found in the 5-CSRT (Higgins et al. 2005). The ketamine-induced inhibition of hippocampal NMDA receptors may enhance the firing rate of glutamatergic PFC neurons and impair PFC-dependent functions, including cognitive flexibility (Greene 2001; Homayoun and Moghaddam 2007; Lisman et al. 2008). A high density of the NR2B subunit within the PFC, including infra-limbic regions (Wenzel et al. 1995), confirmed by autoradiography with [3H]-Ro 25-6981 (Mutel et al. 1998), suggests that the compound exerted its actions in the PFC. It is likely that the unique localization of the NR2B-containing NMDA receptors allows for the reversal of the ketamine-induced cognitive deficit in ASST via blockade of glutamatergic cortical disinhibition. Future studies will reveal the precise mech- anism of the pro-cognitive action of this NR2B-selective NMDA antagonist. Acknowledgments This study was supported by statutory activity funds from the Institute of Pharmacology, Polish Academy of Sciences (Kraków, Poland) and by the project UDA-POIG.01.03.01- 12-063/09-00 Prokog co-financed by the European Union from the European Fund of Regional Development (EFRD). The financial support of the Foundation for Polish Science to T. Kos is highly appreciated. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. 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