| Project/Area Number |
12480233
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Metropolitan Organization For Medical Research |
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Principal Investigator |
SORA Ichiro Tokyo institute of Psychiatry, Dept. of Molecular Psychiatry, Chief, 東京都精神医学総合研究所, 副参事研究員 (40322713)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Kazutaka Tokyo institute of Psychiatry, Dept. of Molecular Psychiatry, Researcher, 東京都精神医学総合研究所, 主任研究員 (60281656)
HAGINO Yoko Tokyo institute of Psychiatry, Dept. of Molecular Psychiatry, Research Associate, 東京都精神医学総合研究所, 研究員 (40332382)
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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 |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2001: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥10,300,000 (Direct Cost: ¥10,300,000)
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| Keywords | Transgenic Knockout Mice / analgesia / reward / Tolerance / opioid / 報酬 / 場所条件づけ試験 / 静脈内自己投与試験 |
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| Research Abstract |
Homozygous transgenic knockout mice without μ-opioid receptors lack morphine-induced antinociception, locomotion, tolerance, physical dependence and reward, μ receptors thus appear to play central roles in these morphine actions. Different levels of μ receptor expression are found in different humans and in different animal strains. In vitro studies indicate that some morphine responses that persist after inactivation of as many as 90% of the initial μ receptor complement, while others are attenuated after inactivating many fewer receptors. Varying levels of μ receptor reserve could thus exist in different μ-expressing neuronal populations in vivo. Heterozygous μ receptor knockout mice express half of wild-type μ receptor levels. Heterozygotes display attenuated locomotion, reduced morphine self-administration, intact tolerance, rightward shifts in morphine lethality dose/effect relationships, and variable effects on place preference compared to wild-type mice. They could demonstrate full physical dependence, as measured by naloxone-precipitated abstinence following five days of morphine administration. Nevertheless, these data document substantial influences that individual differences in levels of μ receptor expression could exert on distinct opiate drug effects.
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