1999 Fiscal Year Final Research Report Summary
Pharmacological and molecular mechanisms on amino acid receptor complexes in brain of animal model for drug abuse
| Project/Area Number |
10670889
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | University of Tsukuba |
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Principal Investigator |
SUZUKI Toshihito Associate Professor, Institute of Clinical Medicine, University of Tsukuba, 臨床医学系, 助教授 (10196850)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Takehiko Associate Professor, Faculty of Education, University of Okayama, 教育学部, 助教授 (10291973)
BABA Atsuomi Assistant Professor, Institute of Clinical Medicine, University of Tsukuba, 臨床医学系, 講師 (80292556)
SHIRAISHI Hiroyasu Professor, Institute of Clinical Medicine, University of Tsukuba, 臨床医学系, 教授 (50009651)
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| Project Period (FY) |
1998 – 1999
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| Keywords | GABAィイD2AィエD2 receptor / cocaine / picrotoxin site / subunit mRNA / autoradiography / in situ hybridization / sensitization / schizophrenia |
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| Research Abstract |
The effects of intermittent intraperitoneal (i.p.) administration of cocaine (20 mg/kg) on GABAィイD2AィエD2-benzodiazepine (BZD) receptors labeled by t-[ィイD135ィエD1S] butylbicyclophophorothionate (TBPS), and on several types of mRNA subunits were investigated in rat brain by in vitro quantitative receptor autoradiography and in situ hybridization. Phosphor screen imaging with high sensitivity and a wide linear range of response was utilized for imaging analysis. There was a significant decrease in the level of α1, α6, β2, β3, and γ2 subunits mRNA with no alteration of [ィイD135ィエD1S] TBPS binding in any regions in the brain of rats, at 1 hour following a single injection of cocaine. In chronically treated-animals, the mean scores of stereotyped behavior were increased with the number of injections. The level of β3 subunit mRNA was decreased in the cortices and caudate-putamen, at 24 hours after a final injection of chronic administrations for 14 days. In the withdrawal from cocaine, the frontal cortex and hippocampal complexes showed a significant increase in [ィイD135ィエD1S] TBPS binding and α1 and β3 subunit mRNA in the rats 1 week after a cessation of chronic administration of cocaine. These findings suggest that the disruption of GABAィイD2AィエD2-BZD receptor formation is closely involved in the development of cocaine-related behavioral disturbances. Further studies on the physiological functions on GABAィイD2AィエD2-BZD receptor complex will be necessary for an explanation of the precise mechanisms underlying the acute effects, development of hypersensitization, and withdrawal state of cocaine.
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