Summary
Brain dopamine D-2 receptors were analysed in the caudate nucleus, putamen and nucleus accumbens in 49 patients with different types of neuropathologically verified dementia and in 39 controls by the binding of3H-spiroperidol. The binding was significantly decreased in all brain areas in patients with Alzheimer's disease (AD), while the changes in patients with multi-infarct dementia (MID) or combined dementia (CD) were non-significant. According to a Scatchard analysis, this decrease in binding was due to the reduced number of receptors. On the other hand, the binding of3H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between3H-spiroperidol binding and neuropathological changes were seen only in AD patients in the nucleus accumbens. The nucleus accumbens was also the only brain area in which there was a significant correlation between dopamine D-2 and the number of muscarinic receptors in AD patients. The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia.
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Ball, M. J., Fishman, M., Hachinski, V., Blume, W., Fox., Kral, V. A., Kirshen, A. J., Fox, H., Merskey, H.: A new definition of Alzheimer's disease: a hippocampal dementia. Lanceti, 14–15 (1985).
Bowen, D. M., Smith, C. B., White, P., Davidson, A. N.: Neurotransmitter related enzymes and indexes of hypoxia in senile dementia and other abiotrophies. Brain99, 459–496 (1976).
Carlsson, A., Gottfries, C.-G., Svennerholm, L., Adolffson, R., Oreland, L., Winblad, B., Aquilonius, S.-M.: Neurotransmitters in human brain analyzed post-mortem: changes in normal aging, senile dementia and chronic alcoholism. In: Parkinson's Disease — Current Progress, Problems and Management (Rinne, U. K., Klingler, M., Stamm, G., eds.), pp. 121–133. Amsterdam: Eisevier. 1980.
Cross, A. J., Crow, T. J., Johnson, J. A., Joseph, M. H., Perry, E. K., Perry, R. H., Blessed, G., Tomlinson, B. E.: Monoamine metabolism in senile dementia of Alzheimer-type. J. Neurol. Sci.60, 383–392 (1983).
Cross, A. J., Crow, T. J., Ferrier, I. N., Ferrier, J. A., Markakis, D.: Striatal dopamine receptors in Alzheimer-type dementia. Neurosci. Lett.52, 1–6 (1984).
Davies, P., Maloney, A. J. F.: Selective loss of cholinergic neurons in Alzheimer's disease. Lancetii, 1403 (1976).
Davies, P., Verth, A. H.: Regional distribution of muscarinic acetylcholine receptors in normal and Alzheimer's type dementia brains. Brain Res.138, 385–392 (1978).
Glowinski, J., Tassin, J. P., Thierry, A. M.: The mesocortico-prefrontal dopaminergic neurons. Trends Neurosci.7, 415–418 (1984).
Gottfries, C.-G., Gottfries, I., Roos, B. E.: The investigation of homovanillic acid in the human brain and its correlation to senile dementia. Brit. J. Psychiat.115, 563–574 (1969).
Isaacson, R. L.: Hippocampal damage: effects on dopaminergic systems of the basal ganglia. Int. Neurobiol.25, 339–359 (1984).
Jenni-Eiermann, S., von Hahn, H. P., Honegger, C. G., Ulrich, J.: Studies on neurotransmitter binding in senile dementia. Gerontology30, 350–358 (1984).
Lee, T., Seeman, P., Tourtellotte, W. W., Farley, I. J., Hornykiewicz, O.: Binding of3H-neuroleptics and3H-apomorphine in schizophrenic brains. Nature274, 897–900 (1978).
Leysen, J. E., Niemegeers, C. J. E., Van Nueten, J. M., Laduron, P. M.:3H-ketanserin (R 41468), a selective3H-ligand for serotonin2 receptor binding sites. Molec. Pharmacol.21, 301–314 (1982).
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the folin phenol reagent. J. Biol. Chem.193, 265–275 (1951).
Luabeya, M. K., Maloteaux, J.-M., Laduron, P. M.: Regional and cortical laminar distribution of serotonin S2, benzodiazepine, muscarinic and dopamine D2 receptors in human brain. J. Neurochem.43, 1068–1071 (1984).
Mackay, A. V. P., Iversen, L. L., Rossor, M., Spokes, E., Bird, E., Arregui, A., Creese, I., Snyder, S. H.: Increased brain dopamine and dopamine receptors in schizophrenia. Arch. Gen. Psychiat.39, 991–997 (1982).
MölsÄ, P., Rinne, U. K.: Acid monoamine metabolites of dopamine and serotonin in the cerebrospinal fluid of patients with Alzheimer's disease. In: Biological Psychiatry (Perris, C., Struwe, G., Jansson, B., eds.), pp. 977–981. Amsterdam: Elsevier. 1981.
Owen, F., Cross, A. J., Cross, T. J., Longden, A., Poulter, M., Riley, G. J.: Increased dopamine receptor sensitivity in schizophrenia. Lancetii, 223–226 (1978).
Palmer, A., Sims, N., Bowen, D., Neary, D., Palo, J., Wikström, J., Davison, A.: Monoamine metabolite concentrations in lumbar cerebrospinal fluid of patients with histologically verified Alzheimer's dementia. J. Neurol. Neurosurg. Psychiat.47, 481–484 (1984).
Parkes, J. D., Marsden, C. D., Rees, J. E.: Parkinson's disease, cerebral arteriosclerosis and senile dementia. Quart. J. Med.43, 49–61 (1974).
Pearce, B. R., Palmer, A. M., Bowen, D. M., Wilcock, G. K., Esiri, M. M., Davidson, A. N.: Neurotransmitter dysfunction and atrophy of the caudate nucleus in Alzheimer's disease. Neurochem. Pathol.2, 221–232 (1984).
Perry, E. K., Perry, R. M.: The cholinergic system in Alzheimer's disease. In: Biochemistry of Dementia (Roberts, P. J., ed.), pp. 135–183. Chichester: J. Wiley. 1980.
Pycock, C. J., Kerwin, R. W., Carter, C. J.: Effects of lesion of cortical DA terminals on subcortical dopamine receptors in rats. Nature286, 74–77 (1980).
Reisine, T. D., Fields, J. Z., Yamamura, H. I., Bird, E. D., Spokes, E., Schreiner, P. S., Enna, S. J.: Neurotransmitter receptor alterations in Parkinson's disease. Life Sci.21, 335–344 (1977).
Reisine, T. D., Yamamura, H. I., Bird, E. D., Spokes, E., Enna, S. J.: Pre- and postsynaptic neurochemical alterations in Alzheimer's disease. Brain Res.159, 477–480 (1978).
Riederer, P., Jellinger, K.: Morphological and biochemical changes in the aging brain: pathophysiological and possible therapeutic consequences. Exp. Brain Res., Suppl.5, 158–166 (1982).
Riederer, P., Jellinger, K.: Morphologie und Pathobiochemie der Parkinsonkrankheit. In: Pathophysiologie, Klinik und Therapie des Parkinsonismus (GÄnshirt, H., ed.), pp. 31–50. Basel: Editiones Roche. 1983.
Rinne, J. O., Laakso, K., Lönnberg, P., MölsÄ, P., PaljÄrvi, L., Rinne, J. K., SÄkö, E., Rinne, U. K.: Brain muscarinic receptors in senile dementia. Brain Res.336, 19–25 (1985).
Rinne, U. K., Lönnberg, P., Koskinen, V.: Dopamine receptors in the parkinsonian brain. J. Neural Transm.51, 97–106 (1981).
Scatton, B.: Further evidence for the involvement of D2 but not D1 dopamine receptors in dopaminergic control of striatal cholinergic transmission. Life Sci.31, 2883–2890 (1982).
Seeman, P.: Brain dopamine receptors. Pharmacol. Rev.32, 229–313 (1980).
Seeman, P., Ulpian, C., Wreggert, K. A., Wells, J. W.: Dopamine receptor parameters detected by3H-spiperone depend on tissue concentration: analysis and examples. J. Neurochem.43, 221–235 (1984).
White, P., Hiley, C. R., Goodhart, M. J., Carrasco, L. H., Keet, J. P., Williams, I. E. I., Bowen, D. M.: Neocortical cholinergic neurons in elderly people. Lanceti, 668–671 (1977).
Yates, C. M., Simpson, J., Gordon, A., Maloney, A. F. J., Allison, Y., Ritchie, I. M., Urquhart, A.: Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down's syndrome. Brain Res.280, 119–126 (1983).
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Rinne, J.O., SÄkö, E., PaljÄrvi, L. et al. Brain dopamine D-2 receptors in senile dementia. J. Neural Transmission 65, 51–62 (1986). https://doi.org/10.1007/BF01249611
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DOI: https://doi.org/10.1007/BF01249611