Behavioural Brain Research 151 (2004) 37–46 Research report The T-maze continuous alternation task for assessing the effects of putative cognition enhancers in the mouse L. Spowart-Manning a,∗ , F.J. van der Staay b a Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, UK b CNS Research, Bayer AG, Aprather Weg 18a, 42096 Wuppertal, Germany Received 17 January 2003; received in revised form 11 August 2003; accepted 11 August 2003 Abstract The T-maze continuous alternation task (T-CAT) assesses the spatial exploratory performance in mice. We performed a series of four experiments in order to establish the T-CAT in mice in our laboratory, to replicate published findings, and to investigate the effects of scopolamine and donepezil. In the first experiment, the task was found to be sensitive to differences between mouse strains, corroborating findings reported by Gerlai. HsdWin:CFW1 mice alternated below chance level, C57BL/6JIco and B6D2F 1 /JIco mice performed above chance level, and C57BL/6NTac and 129S6/SvEvTac mice performed at chance level. In the second experiment, donepezil (Aricept, E2020) at the dose of 3 mg/kg p.o. increased the rate of alternations above the level of the vehicle-treated control group in C57BL/6JIco mice, suggesting that this drug can act as cognition enhancer in normal animals. 1 mg/kg scopolamine, administered intraperiteoneally (i.p.), impaired the spontaneous alternation behaviour of the mice. The slightly lower dose of 0.75 mg/kg did not affect alternation performance. The high dose of donepezil (3 mg/kg) was able to antagonise the scopolamine-induced performance deficit. With respect to time to complete a session, the results were inconclusive. In the third experiment, we found that scopolamine, administered i.p. at the dose of 1 mg/kg, or subcutaneously (s.c.) at the dose of 0.1 mg/kg, decreased the rate of spontaneous alternations in C57BL mice in the T-CAT and increased the time to complete a session. Most likely due to adverse side effects induced by the dose of 1 mg/kg scopolamine, 4 out of 10 animals did not complete at least eight free-choice trials during the maximum session duration of 30 min. No such adverse effects were seen after 0.1 mg/kg scopolamine, administered s.c. Finally, we evaluated whether the T-CAT yields replicable results. We conclude that the T-CAT provides a reliable tool for assessing the effects of cognition-modulating treatments in mice. © 2003 Elsevier B.V. All rights reserved. Keywords: T-maze; Cholinesterase inhibitors; Spatial memory; Alzheimer’s disease; Mice 1. Introduction Spontaneous alternation is a measure of exploratory be- haviour, most often evaluated in rodents [27]. Gerlai [11,13] developed a T-maze continuous alternation task (T-CAT) to assess the spatial exploratory performance in mice. Spon- taneous alternation is defined as a visit to the other of the two goal arms of a T-maze than that visited in the previous trial. In order to alternate or avoid a revisit, a mouse must remember the goal arm chosen in the previous trial. The in- formation about the previous visit is stored in the spatial ∗ Corresponding author. Present address: Department of Pharmacology and Therapeutics, Biotechnology Building, Trinity College Dublin, Dublin 2, Ireland. E-mail address: spowartl@tcd.ie (L. Spowart-Manning). working memory [21]. The T-CAT might be suited to assess the effects of putative cognition enhancing and cognition impairing experimental manipulations. Major reason for the modification of the usual T-maze al- ternation task, in which a mouse is put back into the start arm by the experimenter after it had entered one of the two goal arms, was to avoid handling during a session. In a series of experiments, Gerlai showed that this task appears to depend upon normal functioning of the hippocampus, is guided by extra-maze cues, and is sensitive to strain differences [11]. Acetylcholine (ACh) has been examined for its role in spontaneous alternation, with drugs that decrease synaptic transmission. The alternation rate is decreased with scopo- lamine administration to rats [7,16] and mice [1]. Scopo- lamine is a parasympatholytic drug that acts as muscarinic cholinoceptor antagonist and disrupts cognitive processes. 0166-4328/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2003.08.004