1992 Fiscal Year Final Research Report Summary
A Fundamental study on analysis of ECT imaging using model animals of psycho-neuro disorders
| Project/Area Number |
03670542
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Radiation science
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| Research Institution | Kanazawa University |
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Principal Investigator |
MORI Hirofumi Kanazawa Univ., Radioisotope Center, Professor, アイソトープ総合センター, 教授 (90019604)
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| Co-Investigator(Kenkyū-buntansha) |
KIDO Hideki Kanazawa Univ., School of Medicine,Assist. Prof., 医学部付属病院, 講師 (50161518)
MATSUDA Hiroshi Kanazawa Univ., School of Medicine, Assist. Prof., 医学部付属病院, 講師 (90173848)
SHIBA Kazuhiro Kanazawa Univ., Radioisotope Center, Assistant, アイソトープ総合センター, 助手 (40143929)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Emission CT / receptor / autoradiography / animal model / schizophrenia / antipsychotic drugs / radiopharmaceuticals |
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| Research Abstract |
The effects of acute intravenous or chronic subcutaneous haloperidol (HPD) administration on the local cerebral blood flow (LCBF) in 41 regions of the rat brain were studied by means of the quantative autoradiographic N-isopropyl-p- [125-I] iodoamphetamine technique. After acute HPD administrations, the LCBFs decreased in the anterior cingulate cortex, primary motor cortex and primary auditory cortex, and increased the n. habenula. ChronicHPD administration reduced LCBF in the substantia nigra, and increased LCBFs in the n.caudatus-putamen, n.accumbens and n.habenula. No change in LCBF was observed in any cortical region after chronic HPD administratin.
An in vivo receptor binding techniques was applied to evaluate the affinities of and clozapine, risperidone, RMI-81582 and haloperidol for dopamine D1, D2, 5- HT2 receptors in the rat brain with [3-H] -SCH23390, [3-H] -YM-09151-2 and [3-H] -Ketanserine as selective ligands. Time course study of receptor occupancy at 25 to 250 min after i
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ntraperitoneal administrations with the drugs showed higher 5-HT2 occupancies in the frontal cortex and lower D2 occupancies in the striatum of clozapine, riperidone and RMI-81582 than those of haloperidol. The 5-HT2/D2 ratios of occupancy for clozapine, riperidone and RMI-81582 were 6-7 times higher than that for haloperidol. Stable occupancies of D1 were observed only with RMI-81582 and clozapine, the former maintaining the higher occupancy. These results are in agreement with the previous findings obtained under in vitro conditions and may account for some part of the properties of atypical antipsychotic drugs.
A new ligand, an N-p-lodophenethl diaminodithiol (DADT-IPE), an analog of N- isopropl-p-iodoamphetamine (IMP), was synthesized and subsequently complexed with Tc-99m, using stannous chloride as a reducing agent. Two complexes (a and b) were separated from Tc-99m-DADT-IPE by high performance liquid chromatography. Biodistribution studies suggested that Tc-99m-DADT-IPE (a) has characteristics which are suitable for cerebral perfusion imaging. Less
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Research Products
(6 results)
