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Noradrenaline and animal cognitive processes: implications for dementia

  • Paula Moran (a1) and Brian E. Leonard (a1)


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.



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1.Bartus, R T, Dean, R, Beer, B and Lippa, A S. The Cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217 J: 408–17.
2.Perry, E, Tomlinson, B E, Blessed, Get al.Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978, ii: 1457–9.
3.Perry, E, Perry, R, Blessed, Get al.Necropsy evidence of central cholinergic deficits in senile dementia. Lancet 1977; 1: 189.
4.Whitehouse, P J, Price, D L, Clark, A Wet al.Alzheimer's disease: evidence for selective loss of cholinergic neurons in nucleus basalis. Ann Neurol 1981; 10: 122–6.
5.Allain, H, Reymann, J M, Cognez, Pet al.Alzheimer's disease and the cholinergic hypothesis: an overview. In: Bes, A, ed. Senile dementias: early detection. John Libbey Eurotext: 1986.
6.Sherman, K A, Kumar, V, Ashford, J Wet al.Effect of oral physostigmine in senile dementia. In: Strong, Ret al, eds. Central Nervous Disorders of Ageing Clinical Intervention and Research. N.Y.: Raven Press, 1988.
7.Whitehouse, P J. Alzheimer's disease a multi-system disorder. Psychoparm Bull 1987; 23: 1, 1518.
8.Izquierdo, I. The pathogenesis of the amnesia of Alzheimer's disease T.I.P.S. 1987; vol. 8.
9.Palmer, A M, Francis, P T, Benton, J Set al.Presynaptic serotonergic dysfunction in patients with Alzheimer's disease. J Neurochem 1987; 48: 815.
10.Ebinger, G, Bruyland, M, Martin, J Jet al.Distribution of biogenic amines and their catabolites in brains from patients with Alzheimer's disease. J Neurol Sci 1987; 77: 267–83.
11.Gottfries, C G, Roos, B E and Winblad, B. Changes in the brain catecholamines in patients with dementia of the Alzheimer type. Br J Psychiat 1979; 135: 216–33.
12.Hunter, B, Zornester, S F, Jarvik, M Eet al.Modulation of learning and memory. In: Iversen, et al, eds. Handbook of Psychopharmacology, vol. 8. N.Y.: Plenum Press, 1977: 531–77.
13.Mason, S T. Noradrenaline in the brain: Progress in theories of behavioural function. Progr in Neurobiol 1981; 16: 264–95.
14.Anlezark, G M, Crow, T J and Greenway, A P. Impaired learning and decreased cortical norepinephrine after bilateral locus coeruleus lesions. Science 1973; 181: 682–4.
15.Zornester, S F and Gold, M. The locus coeruleus: Its possible role in memory consolidation. Physiol Behav 1976; 16: 331–6.
16.Chrobak, J C, DeHaven, D L and Walsh, T J. Depletion of brain norepinephrine with DSP4 fails to alter acquisition of performance of a radial arm maze task. Behav Neual Biol 1985; 44: 144–50.
17.Sara, S J and Segal, M. Locus Coeruleus in learning and memory retrieval. In: Matthies, , ed. Learning and Memory; Mechanisms of Information Storage in the Nervous System. N.Y.: Pergamon, 1986: 383–8.
18.Doty, B A and Doty, L A. Facilitative effects of amphetamine on avoidance conditioning in relation to age and problem difficulty. Psychopharmacologia; 9: 234–41.
19.Martinez, J L, Vasquez, B J, Rigter, Het al.Attenuation of amphetamine induced enhancment of learning by adrenal demedullation. Brain Res. 1980; 195: 433–43.
20.Gold, P E and Zornester, S F. The Mnemon and its juices: Neuromodulation of memory processes. Behav Neural Biol 38: 151–89.
21.Sara, S J and Devauges, V. Enhancement of cognitive function in the rat by alpha2 antagonists or electrical stimulation of locus coeruleus. Psychopharm 1986; 31.
22.Sara, S J. 1988. Personal communication.
23.Sara, S J. Noradrenergic modulation of selective attention: its role in memory retrieval. In: Olton, , Gamzu, and Corkin, eds. Memory Dysfunctions: an integration of animal and human research from clinical and preclinical perspectives. Ann NY Acad Sci 1985; 444: 178–93.
24.Waterhouse, B D and Woodward, D. Interaction of norepinephrine with cerebrocortical activity evoked by stimulation of somatosensory afferent pathway in the rat. Exp Neurol 1980; 67: 1134.
25.Gold, P E and McGaugh, J L. Endogenous modulators of memory storage processes. In: Carenaza, et al, eds. Psychoneuroendocrinology in reproduction. London: Academic Press, 1978.
26.Wolkowitz, O M, Tinklenberg, J R and Weingarter, H A. Psychopharmacological perspectives of cognitive functions. Neuropsychobiol 1985; 14: 133–56.
27.Kety, S S. Brain catecholamines, affective states and memory. In: McGaugh, J L ed. The chemistry of mood, motivation and memory. N.Y.: Plenum Press, 1971: 6580.
28.Leslie, F M, Loughlin, S E, Sternberg, O B, McGaugh, J L. Noradrenergic changes and memory loss in mice. Brain Res. 1985 359: 292–9.
29.Goodrick, C L. Learning retention and extinction of a complex maze habit for mature young and senescent wistar albino rats. J Gerontol 1968; 23: 298304.
30.Bartus, R T, Fleming, D and Johnson, H R. Ageing in the rhesus monkey: debilitating effects on short term memory. J Gerontol 1978; 33: 858–71.
31.Dunnett, S B, Evenden, J L, Iversen, S. Delay dependent short term memory deficits in aged rats. Psychopharm 1988; 96: 174–80.
32.Arnsten, A F and Goldman-Rakic, P. Selective prefrontal cortical projections to the region of the loocus coeruleus and raphe nucleii in the rhesus monkey. Br Res 1984; 306: 918.
33.Goldman-Rakic, P S and Arnsten, A F T. Adrenergic agonists are cognitive enhancers in non-human primates. Clin Neuropharm 9, suppl 4: 292–4.
34.Hock, F J. Drug influences on learning and memory in aged animals and humans. Neuropsychobiol 1987; 17: 145–60.
35.McGeer, E G. Ageing and neurotransmitter metabolism in the human brain. Ageing 1978; 7.
36.Vijayashankar, N and Brody, H. A quantitative study of the pigmental neurons in the nuclei locus coeruleus and subcoeruleus in man as related to ageing. J Neuropath Exp Neurol 1979; 38: 490–7.
37.Bondareff, W, Mountjoy, C Q and Roth, M. Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Neurol 1982; 32: 164–8.
38.Berger, B, Tassin, J, Rancurel, Get al.Catecholaminergic innervation of the human cerebral cortex in presenile and senile dementia: Histochemical and biochemical studies. In: Usdin, et al, eds. Enzymes and neurotransmitters in mental disease. Chichester: John Wiley, 1980: 317–28.
39.Iversen, L, Rossor, M, Reynolds, Get al.Loss of pigmented dopamine-beta-hydroxylase positive cells from locus coeruleus in senile dementia of the Alzheimer's type. Neurosci Lett 1983; 39: 95100.
40.Cross, A, Crowe, T, Perry, Eet al.Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease. Br Med J 1981; 282: 93–4.
41.Gottfries, C, Adolfsson, R, Aquiloniuss, Set al.Biochemical changes in dementia disorders of Alzheimer's type. Neurobiol Ageing 1983; 4: 261–71.
42.Mann, D, Yates, P and Marcynink, B. A comparison of changes in the nucleus basalis and locus coeruleus in Alzheimer's disease. J Neurol Neurosurg Psychiat 1984; 47: 201–3.
43.Decker, M W and Gallagher, M. Scopolamine disruption of radial arm maze performance, modification by noradrenergic depletion. Br Res 1987; 417: 5969.
44.Moran, P and Leonard, B E. Effects of DSP4 pretreatment on scopolamine induced amnesia in the rat (abstract). J Psychopharm 1988; 2: 2.
45.Hollander, E, Mohs, R and Davis, K. Cholinergic approaches to the treatment of Alzheimer's disease. 1986. B Med Bull 42; 1: 97100.
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Irish Journal of Psychological Medicine
  • ISSN: 0790-9667
  • EISSN: 2051-6967
  • URL: /core/journals/irish-journal-of-psychological-medicine
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