| Project/Area Number |
12670924
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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 University of Tsukuba, Institute of Clinical Medicine, Psychiatry, Associate Professor, 臨床医学系, 助教授 (10196850)
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| Co-Investigator(Kenkyū-buntansha) |
BABA Atsuomi University of Tsukuba, Institute of Clinical Medicine, Psychiatry, Assistant Professor, 臨床医学系, 講師 (80292556)
HORI Takafumi University of Tsukuba, Institute of Clinical Medicine, Psychiatry, Assistant Professor, 臨床医学系, 講師 (40241822)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | cocaine / phencyclidine / glutamate / GABA / receptor subunit / behavioral sensitization / drug abuse / Drug abuse / Cocaine / NMDA receptor / GABAB receptor / Benzo diazepine / Receptor subunit / in situ hybridization |
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| Research Abstract |
Chronic use of cocaine or phencyclidine can result in the induction of a psychotic state resembling paranoid schizophrenia. Behavioral sensitization resulting from repeated administration of cocaine has been well documented in animal experiments. While dopaminergic systems may be responsible for the development of sensitization, glutamatergic or GABAergic neural system also influences these behavioral abnormalities. We investigated the effects of intraperitoneal administration of cocaine or phencyclidine on the mRNA levels of ionotropic or metabotropic glutamate receptor and GABA receptor subunits in rat brain. As a result, (1) The amount of the NR1 subunit mRNA of the NMDA receptor significantly increased in the hippocampus following a single administration of cocaine (20 mg/kg). Chronic cocaine administration caused a reduction in the level of NR1 subunit mRNA in the striatum and an increase in the hippocampus. (2) A level of α1, β2, β3, γ2 subunit of GABA-benzodiazepine complex was decreased in the cortex and hippocampus following a single injection of cocaine. In chronically treated rats, the level of β3 subunit of GABA-BZD receptor was significantly reduced in the cortex and caudate-putamen. In addition, the nucleus accumbens, hippocampus and thalamus showed a significant increase in the level of GABAB(1) mRNA following repeated administration of cocaine. (3) After repeated phencyclidine administration, mGluR2 and mGluR4 mRNA expression was significantly decreased in the cortex, while a single administration resulted in a decrease in the mGluR mRNA in the cortex. These findings suggested that single and repeated administration of cocaine and phencyclidine independently regulate the mRNA expression of subunits of glutamate and GABA-BZD receptors in the brain.
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