title: Dose-dependent effect of donepezil administration on long-term enhancement of visually evoked potentials and cholinergic receptor overexpression in rat visual cortex.
abstract: Stimulation of the cholinergic system tightly coupled with periods of visual stimulation boosts the processing of specific visual stimuli via muscarinic and nicotinic receptors in terms of intensity, priority and long-term effect. However, it is not known whether more diffuse pharmacological stimulation with donepezil, a cholinesterase inhibitor, is an efficient tool for enhancing visual processing and perception. The goal of the present study was to potentiate cholinergic transmission with donepezil treatment (0.5 and 1mg/kg) during a 2-week visual training to examine the effect on visually evoked potentials and to profile the expression of cholinergic receptor subtypes. The visual training was performed daily, 10min a day, for 2weeks. One week after the last training session, visual evoked potentials were recorded, or the mRNA expression level of muscarinic (M1-5) and nicotinic (α/β) receptors subunits was determined by quantitative RT-PCR. The visual stimulation coupled with any of the two doses of donepezil produced significant amplitude enhancement of cortical evoked potentials compared to pre-training values. The enhancement induced by the 1mg/kg dose of donepezil was spread to neighboring spatial frequencies, suggesting a better sensitivity near the visual detection threshold. The M3, M4, M5 and α7 receptors mRNA were upregulated in the visual cortex for the higher dose of donepezil but not the lower one, and the receptors expression was stable in the somatosensory (non-visual control) cortex. Therefore, higher levels of acetylcholine within the cortex sustain the increased intensity of the cortical response and trigger the upregulation of cholinergic receptors.
authors.affiliation: Laboratoire de Neurobiologie de la Cognition Visuelle, École d'optométrie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Mira
authors.initials: M
authors.lastname: Chamoun
authors.affiliation: Laboratoire de Neurobiologie de la Cognition Visuelle, École d'optométrie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Marianne
authors.initials: M
authors.lastname: Groleau
authors.affiliation: Laboratoire de Neurobiologie de la Cognition Visuelle, École d'optométrie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Menakshi
authors.initials: M
authors.lastname: Bhat
authors.affiliation: Laboratoire de Neurobiologie de la Cognition Visuelle, École d'optométrie, Université de Montréal, Montréal, Québec, Canada. Electronic address: elvire.vaucher@umontreal.ca.
authors.forename: Elvire
authors.initials: E
authors.lastname: Vaucher
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D000077265:Donepezil; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D007189:Indans / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011950:Receptors, Cholinergic / Q000235:genetics*; D011978:Receptors, Nicotinic; D014793:Visual Cortex / Q000187:drug effects*
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D000077265:Donepezil
keywords: Acetylcholinesterase inhibitors; Cholinergic enhancement; Cortical activity; Muscarinic receptors; Nicotinic receptors; Visual cortex