Acute effects of donepezil on visuoespatial abilities

• Grant number: 07/00382-0
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2007
• End date: April 30, 2009
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Sabine Pompéia
• Grantee: Sabine Pompéia
• Host Institution: Departamento de Psicobiologia. Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

It has long been known that the central cholinergic system is implicated in cognitive functioning including visuospatial abilities. There are conflicting results surrounding the capacity of the acetylcholinesterase inhibitor donepezil in causing increases in visuospatial performance of healthy volunteers. This has major implications for understanding the role of the cholinergic system in cognition, and may aid in the development of the clinical use of this drug which is one of the most commonly prescribed treatments for disorders such as Alzheimers disease. Differences between studies of acute donepezil effects may be related to this drugs kinetics, since the time after administration when effects were assessed varied. In particular, no study to date has evaluated acute donepezil cognitive effects at the time of maximum concentration (Tmax), when peak levels of donepezil are reached. Objective: to investigate the time-course of acute effects of donepezil and scopolamine on visuospatial abilities in young healthy subjects. Methods: A double-blind, placebo-controlled, randomized study including 36 young, healthy volunteers. Subjects will received one of three treatments: placebo, donepezil (5 mg p.o.), or the anticholinergic scopolamine (1.2 mg p.o.), included to control for sensitivity of the test battery to cholinergic effects. Treatments will be administered following a double-dummy schedule in such as way that the two post-treatment testing sessions coincided with: 1) the time at which donepezil was mostly tested in previous studies (90 min. after administration) and Tmax for scopolamine (60 min. after treatment); and 2) Tmax for donepezil (210 min. after donepezil intake). Subjects will be presented with classical performance control tests (e.g. DSST, immediate and delayed recall of prose), tasks that evaluate the three main working memory subsystems (digit span and Corsi block test, forward and backward), memory for object locations, tests of 5 spatial abilities, and visual inspection time (IT). (AU)