Measurement of dopamine D2-like receptors in postmortem CNS and pituitary: differential regional changes in schizophrenia.
In situ radioligand binding with autoradiography and anti-human dopamine D(2) receptor antibodies with Western blots have been used to measure the density of dopamine D(2)-like receptors in the caudate-putamen and pituitary from schizophrenic subjects who did or did not have residual antipsychotic drugs in their tissue at death. There was a significant decrease in the Ki for haloperidol displaceable [(125)I]iodosulpride binding in the pituitary (p < 0.01) and caudate-putamen (p < 0.05) from subjects with schizophrenia with residual drugs in their tissue. There was a significant decrease in the density of [(125)I]iodosulpride in the pituitary (p < 0.001) and a strong trend to a decrease in binding in the caudate-putamen (p = 0.055) from subjects with schizophrenia. By contrast, [(3)H]spiperone binding was decreased in the caudate-putamen (p < 0.05) with a trend to decreased binding in the pituitary (p = 0.07) from subjects with schizophrenia. There was no difference in the density of dopamine D(2) receptors in the caudate-putamen from subjects with schizophrenia (p = 0.31). All the findings on receptor densities were independent of drug status. [(125)I]iodosulpride binds to the dopamine D(2&3) receptors. We have shown that there is no change in the dopamine D(2) receptor in the caudate-putamen from subjects with schizophrenia and therefore, these data would be consistent with there being a decrease in the dopamine D(3) in the caudate-putamen from subjects with schizophrenia. Since dopamine D(3) receptors are absent or present at low concentrations in the pituitary, our data would suggest the dopamine D(2) receptor is decreased in that tissue from schizophrenic subjects.
Dean
B
B
The Rebecca L. Cooper Research Laboratory, The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia. bdean@mhri.edu.au
Pavey
G
G
Scarr
E
E
Goeringer
K
K
Copolov
D L
DL
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000494:pharmacology; D001344:Autopsy; D001345:Autoradiography; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013134:Spiperone / Q000378:metabolism; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000378:metabolism
D014150:Antipsychotic Agents; D007457:Iodine Radioisotopes; D017448:Receptors, Dopamine D2; C045105:iodosulpride; D013134:Spiperone; D013469:Sulpiride