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Noradrenaline and animal cognitive processes: implications for dementia

Published online by Cambridge University Press:  13 June 2014

Paula Moran  and
Brian E. Leonard
Paula Moran
Affiliation:
Department of Pharmacology, University College Galway, Galway, Ireland
Brian E. Leonard
Affiliation:
Department of Pharmacology, University College Galway, Galway, Ireland
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Abstract

Recent research on the neurochemical deficits that accompany Alzheimer's disease (AD), senile dementia (SD) and Korsakoff's dementia (KD) have prompted renewed interest in the involvement of central cholinergic systems in learning and memory processes. Evidence for the role of cholinergic systems in the dementias is now overwhelming and has been reviewed in detail elsewhere, e.g. Briefly, such evidence includes findings of decreased cortical activity of the cholinergic marker enzyme choline-acetyltransferase (CAT), reduced activity of the acetylcholine degrading enzyme acetylcholinesterase (AChE), and degeneration of the cholinergic cells of the nucleus basalis of Meynert (nBM) and medial septal nucleus (MS). Pharmacotherapy based on a knowledge of these cholinergic deficits has included (i) ACh precursor therapy, e.g. choline, lecithin; (ii) anti-cholinesterase treatments e.g. physostigmine, tetrahydroaminoacridine (THA), disopropylfluorophosphate (DFP); or (iii) cholinergic synthesis agonists e.g. oxotremorine, arecholine. These have had some success, but it has only been modest. While lack of efficacy has been attributed in specific cases to the pharmacokinetics of some of these drugs e.g. physostigmine, bethanecol, a more general explanation is that SD not only results from a cholinergic deficit but also involves abnormalities in many other neurotransmitter systems.

Thus, more recent findings on the neuropathology of AD and the dementias have implied that while a cholinergic hypothesis of cognitive dysfunction in dementia has strong support, dementia can be considered to be a multi-system disorder. Newer studies indicate pathologies involving serotonergic, dopaminergic, glutaminergic and noradrenergic systems. This review will focus on dysfunction of the noradrenergic system and will conclude that degeneration of this system is an important substrate of cognitive impairments found in dementia.

Type
Perspectives
Information
Irish Journal of Psychological Medicine , Volume 6 , Issue 2 , September 1989 , pp. 106 - 108
Copyright
Copyright © Cambridge University Press 1989

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