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Accession number;02A0472870
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| Title;Methamphetamine-induced gene expression in the brains of developing rats and behavioral sensitization. |
| Author;
MURAOKA SHIN'ICHIRO
(Tokyoishidai Daigakuin Seishinkodoika)
KAJII YASUSHI
(Tokyoishidai Daigakuin Seishinkodoika)
HIRAOKA SHUICHI
(Natl. Inst. of Neurosci.)
FUJIYAMA KO
(Natl. Inst. of Neurosci.)
UMINO ASAMI
(Natl. Inst. of Neurosci.)
NISHIKAWA TOORU
(Tokyoishidai Daigakuin Seishinkodoika)
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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.34-38(2002)
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| Figure&Table&Reference;FIG.1, REF.9 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;We have investigated the effects of a schizophrenomimetic drug, methamphetamine(MAP), on gene expression in the neocortex of developing rats and have isolated a novel and developmentally-regulated MAP-responsive rat gene, mrt1(MAP-responsive transcript 1) using an RNA arbitrarily primed PCR technique. The mrt1 gene encodes single PDZ domain-containing proteins around 62kDa. Acute MAP or cocaine injection caused an induction of the alternatively spliced variants of mrt1 encoding the beta isoform(mrt1b) without affecting the expression of those for the alpha isoform(mrt1a). Pretreatment with a D1 receptor antagonist SCH23390 inhibited the ability of MAP to increase neocortical mrt1b expression. Repeated treatment with MAP, but not with SCH23390 plus MAP, induced behavioral sensitization and upregulated basal expression of mrt1b in the neocortex two and three weeks thereafter. The late-developing, cocaine cross-reactive, D1 antagonist-sensitive, and long-lasting nature of MAP-induced mrt1 expression are similar to the pharmacological profiles of behavioral sensitization, suggesting that neocortical mrt1 may be involved in the molecular cascade establishing and/or maintaining stimulant-induced behavioral sensitization, a model of the onset or relapse of stimulant psychosis and schizophrenia. (author abst.) |
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