ORIGINAL INVESTIGATION Scopolamine disrupts place navigation in rats and humans: a translational validation of the Hidden Goal Task in the Morris water maze and a real maze for humans Jan Laczó 1,2 & Hana Markova 1,2 & Veronika Lobellova 3 & Ivana Gazova 1,2 & Martina Parizkova 1,2 & Jiri Cerman 1,2 & Tereza Nekovarova 3,4 & Karel Vales 3,4 & Sylva Klovrzova 5 & John Harrison 6,7 & Manfred Windisch 8 & Kamil Vlcek 3 & Jan Svoboda 3 & Jakub Hort 1,2 & Ales Stuchlik 3 Received: 17 August 2016 /Accepted: 11 November 2016 /Published online: 24 November 2016 # Springer-Verlag Berlin Heidelberg 2016 Abstract Rationale Development of new drugs for treatment of Alzheimer’ s disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. Objectives We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols. Methods We used scopolamine to model cognitive dysfunc- tion similar to that seen in AD and donepezil, a symptomatic medication for AD, to assess its potential reversible effect on this scopolamine-induced cognitive dysfunction. We tested the effects of scopolamine and the combination of scopol- amine and donepezil on place navigation and compared their effects in human and rat versions of the HGT. Place navigation testing consisted of 4 sessions of HGT performed at baseline, 2, 4, and 8 h after dosing in humans or 1, 2.5, and 5 h in rats. Results Scopolamine worsened performance in both animals and humans. In the animal experiment, co-administration of donepezil alleviated the negative effect of scopolamine. In the human experiment, subjects co-administered with scopol- amine and donepezil performed similarly to subjects on pla- cebo and scopolamine, indicating a partial ameliorative effect of donepezil. Conclusions In the task based on the MWM, scopolamine impaired place navigation, while co-administration of donepezil alleviated this effect in comparable animal and hu- man protocols. Using scopolamine and donepezil to challenge place navigation testing can be studied concurrently in ani- mals and humans and may be a valid and reliable model for Jan Laczó, Hana Markova, and Veronika Lobellova contributed equally to this study. * Jan Laczó JanLaczo@seznam.cz * Ales Stuchlik ales.stuchlik@fgu.cas.cz 1 Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 150 06 Prague, Czech Republic 2 International Clinical Research Center, St. Anne’ s University Hospital Brno, Pekarska 53, 656 91 Brno, Czech Republic 3 Department of Neurophysiology of Memory, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic Psychopharmacology (2017) 234:535–547 DOI 10.1007/s00213-016-4488-2 4 National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic 5 Department of Pharmaceutical Technology, Faculty of Pharmacy, Charles University in Prague, Akademika Heyrovskeho 1203, 500 05 Hradec Králové, Czech Republic 6 Metis Cognition Ltd., Park House, Kilmington Common, Warminster, Wiltshire BA12 6QY, UK 7 Imperial College Faculty of Medicine, South Kensington Campus, London SW7 2AZ, UK 8 NeuroScios GmbH, Willersdorferstrasse 6, A-8061 Radegund/ Graz, Austria