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

0474016 - FGÚ 2018 RIV US eng J - Článek v odborném periodiku
Laczó, J. - Marková, H. - Lobellová, Veronika - Gažová, I. - Pařízková, M. - Cerman, J. - Nekovářová, Tereza - Valeš, Karel - Klovrzová, S. - Harrison, J. - Windisch, M. - Vlček, Kamil - Svoboda, Jan - Hort, J. - Stuchlík, Aleš
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.
Psychopharmacology. Roč. 234, č. 4 (2017), s. 535-547. ISSN 0033-3158. E-ISSN 1432-2072
Grant CEP: GA ČR(CZ) GBP304/12/G069; GA MŠMT(CZ) LH14053
Institucionální podpora: RVO:67985823
Klíčová slova: spatial orientation * scopolamine * acetylcholinesterase inhibitor * human * rat
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 3.222, rok: 2017

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. 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. We used scopolamine to model cognitive dysfunction 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 scopolamine and donepezil on place navigation and compared their effects in human and rat versions of the HGT. 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 scopolamine and donepezil performed similarly to subjects on placebo and scopolamine, indicating a partial ameliorative effect of donepezil. In the task based on the MWM, scopolamine impaired place navigation, while co-administration of donepezil alleviated this effect in comparable animal and human protocols. Using scopolamine and donepezil to challenge place navigation testing can be studied concurrently in animals and humans and may be a valid and reliable model for translational research, as well as for preclinical and clinical phases of drug trials.
Trvalý link: http://hdl.handle.net/11104/0271111