Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans

Ellis, Julia R., Ellis, Kathryn A., Bartholomeusz, Cali F., Harrison, Ben J., Wesnes, Keith A., Erskine, Fiona F., Vitetta, Luis and Nathan, Pradeep J. (2006) Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans. International Journal of Neuropsychopharmacology, 9 2: 175-189. doi:10.1017/S1461145705005407

Author Ellis, Julia R.
Ellis, Kathryn A.
Bartholomeusz, Cali F.
Harrison, Ben J.
Wesnes, Keith A.
Erskine, Fiona F.
Vitetta, Luis
Nathan, Pradeep J.
Title Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans
Journal name International Journal of Neuropsychopharmacology   Check publisher's open access policy
ISSN 1469-5111
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1017/S1461145705005407
Open Access Status DOI
Volume 9
Issue 2
Start page 175
End page 189
Total pages 15
Place of publication Cambridge
Publisher Cambridge University Press
Language eng
Subject 111706 Epidemiology
Abstract Functional abnormalities in muscarinic and nicotinic receptors are associated with a number of disorders including Alzheimer’s disease and schizophrenia. While the contribution of muscarinic receptors in modulating cognition is well established in humans, the effects of nicotinic receptors and the interactions and possible synergistic effects between muscarinic and nicotinic receptors have not been well characterized in humans. The current study examined the effects of selective and simultaneous muscarinic and nicotinic receptor antagonism on a range of cognitive processes. The study was a double-blind, placebocontrolled, repeated measures design in which 12 healthy, young volunteers completed cognitive testing under four acute treatment conditions : placebo (P) ; mecamylamine (15 mg) (M); scopolamine (0.4 mg i.m.) (S) ; mecamylamine (15 mg)/scopolamine (0.4 mg i.m.) (MS). Muscarinic receptor antagonism with scopolamine resulted in deficits in working memory, declarative memory, sustained visual attention and psychomotor speed. Nicotinic antagonism with mecamylamine had no effect on any of the cognitive processes examined. Simultaneous antagonism of both muscarinic and nicotinic receptors with mecamylamine and scopolamine impaired all cognitive processes impaired by scopolamine and produced greater deficits than either muscarinic or nicotinic blockade alone, particularly on working memory, visual attention and psychomotor speed. These findings suggest that muscarinic and nicotinic receptors may interact functionally to have synergistic effects particularly on working memory and attention and suggests that therapeutic strategies targeting both receptor systems may be useful in improving selective cognitive processes in a number of disorders.
Keyword Attention
Alzheimer’s disease
Cholinergic system
Muscarinic receptors
Nicotinic receptors
Working memory
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Health and Rehabilitation Sciences Publications
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