Mesolimbic dopamine D3 receptors and use of antipsychotics in patients with schizophrenia. A postmortem study

Arch Gen Psychiatry. 1997 Mar;54(3):225-32. doi: 10.1001/archpsyc.1997.01830150047009.


Background: The pharmacological properties and distribution of a recently cloned member of the dopamine D2 receptor subfamily, the D3 receptor, has led directly to the hypothesis that it may be the target of antipsychotic action.

Methods: To quantify D3 receptors, we characterized the conditions for selective binding of the radioligand iodine 125-labeled (R)-trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)-amino] tetralin ([125I]trans-7-OH-PIPAT) to the human D3 receptor. We then measured by quantitative autoradiography in postmortem tissue the concentration of D3 receptors in the caudal and rostral basal ganglia regions in patients with schizophrenia and control subjects.

Results: We found about 2-fold elevations in the number of D3 receptors in the basal ganglia and ventral forebrain of long-term hospitalized patients with schizophrenia who received no antipsychotic drugs for at least a month before death (n = 7) compared with matched control subjects (n = 15). Patients with schizophrenia receiving antipsychotic drugs less than 72 hours before death (n = 8) had levels similar to those of control subjects. There were no differences in the binding characteristics or affinity of [125I]trans-7-OH-PIPAT binding to D3 receptors between control subjects and patients with schizophrenia.

Conclusion: In contrast to the previously detected elevation of D2 and D4 receptor levels in schizophrenia, elevation of D3 receptor levels in limbic striatum and its efferents observed in patients with schizophrenia may be reduced by antipsychotic drugs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use*
  • Autoradiography
  • Basal Ganglia / chemistry*
  • Basal Ganglia / drug effects*
  • Binding, Competitive
  • Corpus Striatum / chemistry
  • Corpus Striatum / drug effects
  • Dopamine Agonists / metabolism
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / metabolism
  • Dopamine Antagonists / pharmacology
  • Down-Regulation / drug effects
  • Female
  • Humans
  • Iodine Radioisotopes / metabolism
  • Limbic System / chemistry
  • Limbic System / drug effects
  • Male
  • Middle Aged
  • Prosencephalon / chemistry
  • Prosencephalon / drug effects
  • Radioligand Assay
  • Receptors, Dopamine D2 / analysis*
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism*
  • Tetrahydronaphthalenes / metabolism


  • Antipsychotic Agents
  • DRD3 protein, human
  • Dopamine Agonists
  • Dopamine Antagonists
  • Iodine Radioisotopes
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Tetrahydronaphthalenes