Investigation into the efficacy of the acetylcholinesterase inhibitor, donepezil, and novel procognitive agents to induce gamma oscillations in rat hippocampal slices

Spencer, J. P., Middleton, Laura J. and Davies, C. H. 2010. Investigation into the efficacy of the acetylcholinesterase inhibitor, donepezil, and novel procognitive agents to induce gamma oscillations in rat hippocampal slices. Neuropharmacology 59 (6) , pp. 437-443. 10.1016/j.neuropharm.2010.06.005

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Abstract

One of the major neuropathological hallmarks in Alzheimer’s disease (AD) is the loss of cholinergic neurones of the nucleus basalis of Meynert (NbM). This consistent finding gave rise to the ‘cholinergic’ hypothesis of AD and lead to the subsequent development of acetylcholinesterase (AChE) inhibitors; the first class of drug to be approved for the treatment of AD. However, several studies have questioned the efficacy of using AChE inhibitors in AD. In this study we have investigated the ability of two AChE inhibitors, donepezil (Aricept) and physostigmine, to induce gamma oscillatory activity in rat hippocampal slices; network activity believed to play a role in higher cognitive function. We report here that donepezil is capable of inducing gamma oscillations in region CA3 of rat hippocampal slices, which may contribute to its procognitive action. However, donepezil-induced gamma oscillations are weak in comparison to physostigmine. We also explore the activity of novel agents with known procognitive activity, and show that one such agent, the M1 muscarinic acetylcholine receptor agonist, 77-LH-28-1, can significantly enhance donepezil-induced gamma oscillations. These data support the notion that it should be possible to find a more efficacious AChE inhibitor or an adjunctive approach, to provide a better therapeutic intervention in AD.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology
Subjects:	B Philosophy. Psychology. Religion > BF Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Aricept; Cognition; Alzheimer’s Disease; Muscarinic acetylcholine receptor; Serotonin; Hippocampus
Publisher:	Elsevier
ISSN:	0028-3908
Last Modified:	19 Mar 2016 23:08
URI:	https://orca.cardiff.ac.uk/id/eprint/39822

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