Acute effects of donepezil in healthy young adults underline the fractionation of executive functioning

• Published in: Journal of psychopharmacology (Oxford) 2011-11, Vol.25 (11), p.1508-1516
• Main Authors: Ginani, GE, Tufik, S, Bueno, OFA, Pradella-Hallinan, M, Rusted, J, Pompéia, S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Attention - drug effects; Biological and medical sciences; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; Executive Function - drug effects; Human performance; Humans; Indans - pharmacology; Male; Medical sciences; Memory; Memory, Short-Term - drug effects; Neuropharmacology; Neuropsychological Tests; Pharmacology. Drug treatments; Piperidines - pharmacology; Prescription drugs; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychomotor Performance - drug effects; Psychopharmacology; Reaction Time - drug effects; Young Adult; Young adults
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881110391832

The cholinergic system is involved in the modulation of both bottom-up and top-down attentional control. Top-down attention engages multiple executive control processes, but few studies have investigated whether all or selective elements of executive functions are modulated by the cholinergic system. To investigate the acute effects of the pro-cholinergic donepezil in young, healthy volunteers on distinct components of executive functions we conducted a double-blind, placebo-controlled, independent-groups design study including 42 young healthy male participants who were randomly assigned to one of three oral treatments: glucose (placebo), donepezil 5 mg or donepezil 7.5 mg. The test battery included measures of different executive components (shifting, updating, inhibition, dual-task performance, planning, access to long-term memory), tasks that evaluated arousal/vigilance/visuomotor performance, as well as functioning of working memory subsidiary systems. Donepezil improved sustained attention, reaction times, dual-task performance and the executive component of digit span. The positive effects in these executive tasks did not correlate with arousal/visuomotor/vigilance measures. Among the various executive domains investigated donepezil selectively increased dual-task performance in a manner that could not be ascribed to improvement in arousal/vigilance/visuomotor performance nor working memory slave systems. Other executive tasks that rely heavily on visuospatial processing may also be modulated by the cholinergic system.