P1-047: Memantine reverses cognitive deficits induced by total sleep deprivation in O. degus

To date, preclinical models used to assess novel cognitive enhancing therapies have been poor predictors of positive clinical outcome. The Octodon degus expresses neuronal ß-amyloid precursor protein (displaying both intracellular and extracellular deposits of amyloid-ß-peptide), as well as intracellular accumulations of tau-protein and ubiquitin (Inestrosa et al., 2005). Within the frame of IMI PharmaCog European Consortium, we aimed to investigate the effect of sleep deprivation on O. degus cognitive performance to evaluate this as a potential model to assess the cognitive enhancing properties of novel therapeutic agents for Alzheimer's Disease. A total of 20 Octodon degus (3 ± 0.5 years) were randomly divided in 4 groups: control, Memantine (1-amino-3, 5-dimethyladamantane) treated and total sleep deprived with/without Memantine treatment. Total sleep deprivation (TSD) took place for six hours during three consecutive days. After each of these days we tested motor (by using an automated locomotor activity apparatus) and cognitive function (by using Barnes and Radial mazes) of all the animals. Memantine (10 mg/kg/day) or placebo was intraperitoneally administered before each sleep deprivation process. All the sleep-deprived animals showed significant motor and cognitive deficits (p < 0.001) when compared with non-deprived (both control- and Memantine-treated) animals. However, Memantine significantly diminishes (p < 0.01) the time to complete the tasks and the number of errors in both radial and Barnes mazes in sleep deprived O. degus.