Title: Dopamine Receptor Subtypes: Differential Regulatory Characteristics and Levels in Schizophrenia
Abstract: D1 dopamine receptors have not generally been considered to be involved in the mechanism of action of antipsychotic drugs since most potent butyrophenones and substituted benzamide neuroleptics are weak antagonists at this dopamine receptor. Surprisingly, in rodents, both D1 and D2 dopamine receptors have now been shown to mediate similar behavioral responses, while antagonism of either dopamine receptor also produces similar behavioral outcomes. Because such antagonist responses are often predictive of antipsychotic activity, my collaborators and I have investigated the radioligand binding properties of dopamine receptors in postmortem brains from schizophrenic patients (Hess et al., 1987a). Brain tissue from 8 control and 8 schizophrenic patients (as diagnosed by the primary physician) was obtained from the District of Columbia Medical Examiners Office, Washington, DC. Chart review by a research psychiatrist (J.E.K.) confirmed the D.S.M.-III diagnosis of schizophrenia in 6 patients. The two additional patients had chronic non-remitting psychotic illnesses which started at ages 46 and 62. The brains were removed (postmortem intervals: control = 16.1 +/− 1.7 hours, schizophrenic = 21.1 +/− 4.9 hours), the caudate nucleus dissected on ice, frozen whole in liquid nitrogen, pulverized and then stored in small, airtight plastic bags at −70°C until assayed. D1 dopamine receptor affinities and densities were assessed by 3H-SCH23390 binding. D2 dopamine receptor properties were assessed by 3H-spiperone binding, assayed in the presence of 40 nM ketanserin to mask its binding to S2 serotonin receptors.
Publication Year: 1988
Publication Date: 1988-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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