Dopamine D2 -Receptors in Post-mortem Human Brains from Schizophrenic Patients

  • J. Kornhuber
  • P. Riederer
  • G. P. Reynolds
  • H. P. Beckmann
  • K. Jellinger
  • E. Gabriel


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.


Dopamine Receptor Schizophrenic Patient Tardive Dyskinesia Neuroleptic Drug Spiperone Binding 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • J. Kornhuber
    • 1
  • P. Riederer
    • 1
  • G. P. Reynolds
    • 2
  • H. P. Beckmann
    • 1
  • K. Jellinger
    • 3
  • E. Gabriel
    • 4
  1. 1.Department of PsychiatryUniversity of WürzburgGermany
  2. 2.Department of PathologyUniversity of NottinghamUK
  3. 3.Ludwig Boltzmann Institute for Clinical NeurobiologyViennaAustria
  4. 4.Psychiatric Hospital BaumgartnerViennaAustria

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