Dopamine D2 -Receptors in Post-mortem Human Brains from Schizophrenic Patients
The currently predominant biological hypothesis of schizophrenia is the dopamine hypothesis. It is based mainly on the fact that most antipsychotic drugs possess a common ability to block central dopamine D2 receptors, implying a hyperactive dopaminergic system in schizophrenia. There is little direct evidence for overactive dopaminergic neurons in schizophrenia. Thus in recent years the alternative hypothesis of changed post-synaptic dopamine receptors has been investigated. Dopamine receptors, as defined by the binding of various ligands, e.g. [3H]spiperone (Owen et al. 1978; Mackay et al. 1982; Seeman et al. 1984; Pimoule et al. 1985; Mita et al. 1986) and [3H]flupenthixol (Cross et al. 1981), were measured at either a single concentration or a range of concentrations to determine maximum number of binding sites (Bmax) and apparent equilibrium dissociation constant (KD). Elevated D2 receptor densities in schizophrenics have been reported in most of these studies, while the D1 receptors were found to be unchanged by most investigators using either a single concentration of [3H] ligand (Cross et al. 1981; Pimoule et al. 1985) or a range of concentrations to determine D1 receptor densities (Seeman et al. 1987). The interpretation of these results, however, remains difficult, since most patients included in these studies had been treated with neuroleptic drugs. Long-term neuroleptic administration results in an increase in D2 (Owen et al. 1980; Mackenzie and Zigmond 1985) but not D1 receptors (Mackenzie and Zigmond 1985) in animal experiments. It is possible, therefore, that changes in D2 receptors in schizophrenia are due mainly to chronic neuroleptic treatment.
KeywordsDopamine Receptor Schizophrenic Patient Tardive Dyskinesia Neuroleptic Drug Spiperone Binding
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- Cross AJ, Crow TJ, Owen F (1981) 3H-Flupenthixol binding in post-mortem brains of schizophrenics: evidence for a selective increase in dopamine D2 receptors. Psychopharmacology (Berlin) 74: 122–124Google Scholar
- Cross AJ, Crow TJ, Ferrier IN, Johnson JA, Johnstone EC, Owen F, Owens DGC, Poulter M (1985) Chemical and structural changes in the brain in patients with movement disorders. In: Casey DE, Chase TN, Christensen AV, Gerlach J (eds) Dyskinesia: research and treatment. Berlin Heidelberg New York, Springer pp 104–110’Google Scholar
- Crow TJ, Owen F, Cross AJ, Ferrier N, Johnstone EC, McCreadie RM, Owens DOC, Poulter M (1981) Neurotransmitter enzymes and receptors in post-mortem brain in schizophrenia: evidence that an increase in D2 dopamine receptors is associated with the type I syndrome. In: Riederer P, Usdin E (eds) Transmitter biochemistry of human brain tissue. London, Macmillan, pp 85–96Google Scholar
- Haberland N, Hetey L (1987) Studies in postmortem dopamine uptake. H. Alterations of the synaptosomal catecholamine uptake in postmortem brain regions in schizophrenia. J Neural Transm 68: 303–313Google Scholar
- Herold S, Leenders KL, Turton DR, Kensett MJ, Pike VW, Clark JC, Brooks DJ, Crow TJ, Owen F,Co?per. S, Johnstone EC (1985) Dopamine receptor binding in schizophrenic patients as measured with 1 C- methylspiperone and PET. J Cereb Blood Flow Metab 5: S191 - S192Google Scholar
- Kornhuber J, Riederer P, Reynolds GP, Beckmann H, Jellinger K, Gabriel E (1989) 3H-Spiperone binding sites in post-mortem brains from schizophrenic patients. Relationship to neuroleptic drug treatment, abnormal movements and positive symptoms. J Neural Transm75:1–10Google Scholar
- Mackay AVP, Iversen LL, Rossor M, Spokes E, Bird E, Arregui A, Creese I, Snyder SH (1982) IncreasedGoogle Scholar
- brain dopamine and dopamine receptors in schizophrenia. Arch Gen Psychiatry 39: 991–997 Mackenzie RG, Zigmond MJ (1985) Chronic neuroleptic treatment increases D-2 but not D-1 receptors in rat striatum. Eur J Pharmacol 113: 159–165Google Scholar
- Murugaiati K, Theodorou A, Mann S, 7Clow A, Jenner P, Marsden CD (1982) Chronic continuous administration of neuroleptic drugs alters cerebral dopamine receptors and increases spontaneous dopaminergic action in the striatum. Nature 296: 570–572Google Scholar
- Pimoule C, Schoemaker H, Reynolds GP, Langer SZ (1985) [3H] SCH 23390 labeled D dopamine receptors are unchanged in schizophrenia and Parkinson’s disease. Eur J Pharmacol 114: 235–237Google Scholar
- Seeman P, Bzowej NH, Guan HC, Bergeron C, Reynolds GP, Bird ED, Riederer P, Jellinger K, Tourtellotte WW (1987) Human brain D and D2 dopamine receptors in schizophrenia, Alzheimer’s, Parkinson’s and Huntington’s diseases. Di 1: 5–15Google Scholar
- Wong DF, Wagner HN, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Raven HT, Wilson AA, Toung JKT, Malat J, Williams JA, O’Tuama LA, Snyder SH, Kuhar MJ, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234: 1558–1563PubMedCrossRefGoogle Scholar