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.