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March 1997

Mesolimbic Dopamine D3 Receptors and Use of Antipsychotics in Patients With Schizophrenia: A Postmortem Study

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.

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

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