| Project/Area Number |
01570606
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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 |
Psychiatric science
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| Research Institution | Okayama university |
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Principal Investigator |
OTSUKI Saburo Okayama University, Medical School, Professor, 医学部, 教授 (80033041)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Toshiki Okayama University, Medical School Hospital, Assistant Professor, 医学部附属病院, 助手 (30181019)
AKIYAMA Kazufumi Okayama University, Medical School Hospital, Assistant, Professor, 医学部附属病院, 助手 (40150990)
柏原 健一 岡山大学, 医学部附属病院, 助手 (80204387)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Methamphetamine / Cocaine / Reverse tolerance / Behavioral sensitization / Striatum / D-1 receptor / D-2 receptor / 脳内透析法 / ドパミン / SCH23390 / YMー09151ー2 / 交差逆耐性 / ラット |
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| Research Abstract |
The present study examined behavioral and biochemical alterations in methamphetamine (MAP) or cocaine-induced Behavioral Sensitization (BS). Enhancement of striatal dopamine (DA) eflux was observed in animals sensitized by chronic cocaine administration in response to a challenge of either cocaine (20 mg/kg) or MAP (4 mg/kg). These lines of evidence indicate that enhanced DA efflux in MAP-induced behavioral sensitization and cross behavioral sensitization between MAP and cocaine may be related to altered function of Na^+-dependent DA uptake carrier complex on which cocaine acts as an inhibitor. The effect of co-administration of SCH-23390 or YM-09151-2 prior to each MAP injection on DA efflux in the striatal perfusates was investigated. Animals in MAP-group were treated with MAP (4 mg/kg) for the first 7 days, and with MAP (8 mg/kg) for the subsequent 7 days. SCH 23390 + MAP group and YM-09151-2 + MAP group were treated with SCH 23390 (0.5 mg/kg) and YM-09151-2 (1 mg/kg), respectively, 5 min prior to each MAP injection for 14 days. MAP was injected in the same manner as in the MAP group. After an abstinence period of three months, a challenge of MAP (4 mg/kg) alone produced augmented stereotypy in the MAP-group, but not in the control, SCH 23390 + MAP, or YM-09151-2 + MAP groups. In parallel with this behavioral observation, the degree to which striatal DA efflux increased following the MAP challenge was significantly greater in the MAP group than in the salinetreated control, SCH 23390 + MAP or YM-09151-2 + MAP groups. While DA efflux did not differ significantly in intensity between the control and YM-09151-2 + MAP group, it was slightly, but significantly, greater in the SCH 23390 + MAP group than in the control.
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