Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans.
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, placebo-controlled, 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.
Ellis
Julia R
JR
Behavioural Neuroscience Laboratory, Department of Physiology, Monash Centre for Brain and Behaviour, Monash University, Melbourne Australia.
Ellis
Kathryn A
KA
Bartholomeusz
Cali F
CF
Harrison
Ben J
BJ
Wesnes
Keith A
KA
Erskine
Fiona F
FF
Vitetta
Luis
L
Nathan
Pradeep J
PJ
D000328:Adult; D000704:Analysis of Variance; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D021641:Recognition, Psychology / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology; D013997:Time Factors
D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D012601:Scopolamine