Mesolimbic Dopamine D3 Receptors and Use of Antipsychotics in Patients With Schizophrenia

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Abstract
Background: The pharmacological properties and distribution of a recently cloned member of the dopamine D2receptor subfamily, the D3receptor, has led directly to the hypothesis that it may be the target of antipsychotic action. Methods: To quantify D3receptors, 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 D3receptor. We then measured by quantitative autoradiography in postmortem tissue the concentration of D3receptors 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 D3receptors 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 D3receptors between control subjects and patients with schizophrenia. Conclusion: In contrast to the previously detected elevation of D2and D4receptor levels in schizophrenia, elevation of D3receptor levels in limbic striatum and its efferents observed in patients with schizophrenia may be reduced by antipsychotic drugs.