SUBJECT: MESOLIMBIC DOPAMINE D(3) RECEPTORS AND USE OF ANTIPSYCHOTICS IN PATIENTS WITH SCHIZOPHRENIA SOURCE:

ABSTRACTS OF Archives of General Psychiatry DATE: March 15, 1997 -

A Postmortem Study

Background: The pharmacological properties and distribution of a recently cloned member of the dopamine D(2) receptor subfamily, the D(3) receptor, has led directly to the hypothesis that it may be the target of antipsychotic action.

Methods: To quantify D(3) 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 ([[125]I]trans -7- OH-PIPAT) to the human D(3) receptor. We then measured by quantitative autoradiography in postmortem tissue the concentration of D(3) 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 D(3) 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 [[125]I]trans -7-OH-PIPAT binding to D(3) receptors between control subjects and patients with schizophrenia.

Conclusion: In contrast to the previously detected elevation of D(2) and D(4) receptor levels in schizophrenia, elevation of D(3) receptor levels in limbic striatum and its efferents observed in patients with schizophrenia may be reduced by antipsychotic drugs.

Copyright 1997 American Medical Association. All Rights Reserved.

AUTHOR(S): Eugenia V. Gurevich, PhD; Yvette Bordelon; Raymond M. Shapiro, MD, PhD; Steven E. Arnold, MD; Raquel E. Gur, MD; Jeffrey N. Joyce, PhD

SOURCE: Archives of General Psychiatry, March, 1997


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