부산대학교 도서관

Using an indirect subtraction binding technique and human postmortem tissue, several laboratories reported finding increases in dopamine D[sub 4] receptors in caudate nuclei of schizophrenic patients, although others have not replicated these findings. NGD-94-1 is a selective D[sub 4] antagonist with low affinity for the D[sub 2] and D[sub 3] receptors. [³H]NGD-94-1 has been used in this study to directly determine the density of D[sub 4] receptors in normals (n = 13) and schizophrenic subjects (n = 7) off antipsychotic drugs for at least 3 months prior to death, or on antipsychotic (n = 7) drugs at the time of death. Human postmortem coronal brain sections were incubated with [³H]NGD-94-1 and autoradiograms developed; and binding in pertinent regions was quantified. In normals, the highest density of [³H]NGD-94-1 binding was in the hippocampus (68 fmol mg[sup -1], temporal (33), insular (30), and entorhinal cortices (24.9). Significant increases in [³H]NGD-94-1 density in schizophrenics (n = 14) vs normals (n = 13) were observed in the entorhinal cortex (46%) at both low and high magnifications. The increases observed in the schizophrenics were found in both schizophrenics off antipsychotic drugs for at least 3 months prior to death and those on antipsychotic drugs at the time of death. Thus, the changes may be disease-related and not a consequence of pharmacological treatment. No significant differences were found between the two schizophrenic groups in any brain area studied. [ABSTRACT FROM AUTHOR]