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A Postmortem Study

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

Arch Gen Psychiatry. 1997;54(3):225-232.

Abstract
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'-iodo2'-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 fore brain 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.

Author Affiliations
From the Departments of Psychiatry (Drs Gurevich, Shapiro, Arnold, Gur, and Joyce) and Pharmacology (Ms Bordelon and Dr Joyce), University of Pennsylvania School of Medicine, Philadelphia. Drs Gurevich and Joyce are now at the William T. Christopher Center for Parkinson's Disease Research, Sun Health Research Institute, Sun City, Ariz.

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