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Accession number;02A0472898
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| Title;Molecular genetics of opioid analgesia and reward. |
| Author;
SORA ICHIRO
(Psychiatr. Res. Inst. of Tokyo)
IKEDA KAZUTAKA
(Psychiatr. Res. Inst. of Tokyo)
IDE SOICHIRO
(Psychiatr. Res. Inst. of Tokyo)
HATA HARUMI
(Yokohamashidai In Sogorigaku)
SHINOHARA KEIKO
(Psychiatr. Res. Inst. of Tokyo)
YAMAMOTO TOSHIFUMI
(Mol Neurobiol Nida/nih, Usa)
()
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Journal Title;Annual Report of the Pharmacopsychiatry Research Foundation
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Journal Code:Y0939A
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ISSN:0286-7591
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VOL.;NO.34;PAGE.221-228(2002)
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| Figure&Table&Reference;FIG.7, REF.22 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Homozygous transgenic knockout mice without .MU.-opioid receptors lack morphine-induced antinociception, locomotion, tolerance, physical dependence and reward. .MU. receptors thus appear to play central roles in these morphine actions. Different levels of .MU. 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 .MU. receptor complement, while others are attenuated after inactivating many fewer receptors. Varying levels of .MU. receptor reserve could thus exist in different .MU.-expressing neuronal populations in vivo. Heterozygous .MU. receptor knockout mice express half of wild-type .MU. 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 .MU. receptor expression could exert on distinct opiate drug effects. (author abst.) |
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