Affiliations: [a] Department of Molecular and Medical Genetics, Program in Neuroscience, University of Toronto, Toronto, Canada | [b] Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada | [c] University of British Columbia, Okanagan Campus, Kelowna, Canada
Correspondence:
[*]
Correspondence to: Bechara J. Saab, Brain Research Institute, Swiss Federal Institute of Technology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Tel.: +41 44 635 3309; Fax: +41 44 635 3303; E-mail: [email protected].
Note: [1] These authors contributed equally to the manuscript.
Abstract: Alzheimer's disease (AD) is multi-factorial mental disorder characterized by a copious array of congruent features cumulating in disrupted memory and dysthymia. Though the mechanism remains elusive, the highly unspecific pharmaceutical, memantine, provides modest benefits for patients with moderate-to-severe AD. A greater understanding of how memantine affects cognitive function promises to facilitate the search for better therapeutics. We therefore examined cognitive flexibility of mice following 5 and 10 mg/kg memantine administration using a platform re-location water maze. Strikingly, subjects receiving memantine demonstrated memory impairment relative to controls when re-trained off drug, revealing a novel and unusual disruption of cognitive flexibility.
