| Project/Area Number |
62480243
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Tokyo Medical and Dental University (1989)
Shinshu University (1987-1988) |
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Principal Investigator |
TORU Michio Tokyo Medical and Dental University, School of Medicine, Department of Neuropsychiatry, Professor and Chairman, 医学部, 教授 (20013972)
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| Co-Investigator(Kenkyū-buntansha) |
KURUMAJI Akeo Tokyo Medical and Dental University, School of Medicine, Department of Neuropsyc, 医学部, 医員
KOBAYASHI Toshio Shinshu University, School of Medicine, Department of Psychiatry, Lecturer, 医学部, 助手
HATA Norio Shinshu University, School of Medicine, Department of Psychiatry, Lecturer, 医学部, 助手
SHIMIZU Hiromitsu Shinshu University, School of Medicine, Department of Psychiatry, Lecturer, 医学部, 助手
OGATA Hiroshi Shinshu University, School of Medicine, Department of Psychiatry, Associate Prof, 医学部, 助教授 (30020861)
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| Project Period (FY) |
1987 – 1989
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| Keywords | chronic schizophrenia / dopamine uptake sites / benzodiazepine receptors / NMDA receptors / glutamic acid / dopamine / substance P / methionine-enkaphalin |
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| Research Abstract |
In the analysis of post-mortem brains of 14 chronic schizophrenic patients and 10 controls, we measured the uptake sites of dopamine, benzodiazepine receptors and N-methyl-D-aspartate(NMDA) receptors. Dopamine uptake sites were measured by using ^3-GBR 12935 and a significant increase of specific binding was found in the schizophrenic putamen but not in the caudate. Benzodiazepine receptors, which have never measured in the schizophrenic brain, were analyzed by specific ^3-flunitrazepam binding to 12 brain areas. We found increased specific binding in schizophrenic group to 3 areas of the prefrontal cortex, 2 areas of the temporal cortex and cornu Ammonis. The specific ^3-flunitrazepam binding values positively correlate with GABA contents, the specific ^3-kainate binding values, tyrosine hydroxylase activity, Bmax values of dopamine D2 binding and substance P immunoreactivity while they negatively correlate with glutamic acid contents. ^3-MK801 was used to label the NMDA receptors. Am
… More
ong 14 brain areas assayed, the specific ^3-MK801 binding was significantly increased in the superior temporal gyrus, the superior parietal cortex and the supra-marginal cortex of schizophrenic patients. The ^3-MK801 binding values positively correlate with ^3-kainate binding values, Bmax values of D2 binding, tyrosine hydroxylase activity, substance P, methionine-enkephalin and CCK-8 immunoreactivity while they negatively correlate with glutamic acid contents.
These results suggest that several neuropeptides such as substance P, methionine-enkephalin and CCK-8 function with dopaminergic hyperactivity in the same direction resulting hypofunction of glutamatergic neurons. Subcortical hypoglutamatergic states might induce supersensitivity of glutamate receptors as shown in the increase of ^3-kainate and ^3-MK801 binding. Since these results were obtained from chronic schizophrenic brains, one possibility of developing new drugs to treat chronic states of schizophrenia could be to activate glutamat ergic neurons in the brain. Less
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