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


CONCLUSIONS
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.
Gurevich
E V
EV
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, USA.
Bordelon
Y
Y
Shapiro
R M
RM
Arnold
S E
SE
Gur
R E
RE
Joyce
J N
JN
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001345:Autoradiography; D001479:Basal Ganglia / Q000737:chemistry* / Q000187:drug effects*; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008032:Limbic System / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016548:Prosencephalon / Q000737:chemistry / Q000187:drug effects; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000187:drug effects* / Q000378:metabolism; D050637:Receptors, Dopamine D3; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007457:Iodine Radioisotopes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes