Dopamine D₄ receptors and effects of guanine nucleotides on [³H]raclopride binding in postmortem caudate nucleus of subjects with schizophrenia or major depression

The densities of dopamine-D₄ receptors were determined in postmortem samples of caudate nucleus from patients with schizophrenia (n = 9) and age-matched controls (n = 10). D₄ receptor binding was defined as the defined as the difference between binding sites labeled by [³H]YM-09151-2 (D₂ + D₃ + D₄ receptors) and those by [³H]raclopride, in the presence of 5′- guanylylimidodiphosphate (Gpp(NH)p) (D₂ + D₃ receptors). D₄ receptor binding was measurable in all the subjects with schizophrenia (mean = 3.8 pmol/ g tissue) but only in 3/10 controls. To determine the specificity of these findings for schizophrenia, D₄ receptor binding was also measured in the caudate nucleus of suicide victims with major depression (n = 6) and age-matched controls (n = 6). A small amount of D₄ binding was noted in some of the controls + depressed subjects and there was no significant difference between controls and patients with major depression. The addition of 200 μM Gpp(NH)p to the assay significantly increased the amount of specific binding of [³H]raclopride in control tissues, but not in tissues from subjects with schizophrenia, suggesting an abnormality in the G-protein component coupled to the D₂ receptor. [³H]Raclopride binding was also significantly increased by Gpp(NH)p in subjects with major depression. These results confirm a previous report of Seeman et al. (1993) and suggest that measurable D₄ receptor binding in the caudate nucleus is more frequent in patients with schizophrenia as compared with normal controls and subjects with major depression and that guanine nucleotides do not enhance [³H]raclopride binding in schizophrenia. Further study is needed to determine if D₄ binding is increased and if an abnormality in the G-protein component coupled to the D₂ receptor is present in other brain areas in schizophrenia.