1990 Fiscal Year Final Research Report Summary
Biochemical and Pharmacological Research on Affective Disorders from the Aspect of the Mechanism of Neural Transmission and Intracellural Signal Transduction
| Project/Area Number |
63304044
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Gunma University Scholl of Medicine (1989-1990)
Saitama Medical University (1988) |
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Principal Investigator |
HIGUCHI Teruhiko Gunma University School of Medicine, Associate Prof., 医学部, 助教授 (90105883)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBUYA Haruo Tokyo Medical and Dental University Faculty of Medicene, Lecturer, 医学部, 講師 (10158959)
KOYAMA Tsukasa Hokkaido University School of Medicene, Associate Prof., 医学部, 助教授 (10113557)
NOMURA Soichiro Fujita-Gakuen Health University, Associate Prof., 医学部, 助教授 (80113091)
ASAKURA Mikio St. Marianna University School of Medicine, Associate Prof., 医学部, 助教授 (70103504)
MIKUNI Masahiko National Institute of Neurosciences, Ncnp,, 神経センター神経研究所, 室長 (00125353)
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| Project Period (FY) |
1988 – 1990
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| Keywords | Affective Disorders / Antidepressants / Signal Transduction / Neural Transmission / Serotonin / Catecholamine / Second Messenger |
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| Research Abstract |
The remarkable results in this project are as follows.
1. Antidepressants act directly on the second messenger system of 5HT_2 receptor and the direct action on the GTP binding proteins is considered to be important for the mode of action of antidepressants.
2. Protein kinase C (phospholipid-independent/Ca^<++>-dependent kinase) in rat brain membrane was increased by the chronic treatment with antidepressants. This result indicates that antidepressants may keep the continuous activation of PKC.
3. Ca^<++> response with 5HT in the platelets was investigated in the patients with major depression compared to normal controls. Ca^<++> response was much greater in the patients with major depression than in the controls. This result will support the serotonergic supersensitive theory of depression.
4. Chronic treatment of antidepressants causes enhanced coupling of Gs to adenylate cyclase as well as exerting influence on the interaction of Gs and Gi/o.
The classic monoamine hypothesis of depression in which affective disorders are associated with the decrease of NE or 5HT release has been revised in these few years. Recently, the great advances have clarified the second messenger systems and the new direction to study the action for the antidepressants has been shown. In this research project, we found the direct action of antidepressants on the second messenger systems. In addition, in clinical investigation, we found the increased response of second messenger systems in the patients with major depression. Taken together, we present hypothesis that the functional abnormality may exist in the second messenger systems in affective disorders and the action of antidepressants may normalize this abnormality.
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