2014 Fiscal Year Final Research Report
Elucidation of epigenetic regulation of alcohol dependence
Project/Area Number |
25860394
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Applied pharmacology
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Research Institution | Sapporo Medical University |
Principal Investigator |
MIZUO Keisuke 札幌医科大学, 医学部, 助教 (90459735)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Keywords | アルコール / PP2A / Cdk5 / HDAC5 |
Outline of Final Research Achievements |
The mice chronically treated with ethanol revealed severe withdrawal signs. Under these conditions, the expression of Cdk5 was significantly increased in limbic forebrain. The i.c.v. treatment of roscovitine, a Cdk5 inhibitor, during chronic ethanol treatment was completely blocked the development of ethanol dependence. Ten days after withdrawal, we performed a conditioned place preference to evaluate ethanol relapse. At the dose of 0.5 g/kg of ethanol, which produced neither preference nor aversion in control group, the alcohol group showed significant rewarding effects. PP2A was increased in limbic forebrain (containing nucleus accumbens) at ethanol relapse state. Moreover,i.c.v. treatment of the PP2A inhibitor cantharidic acid during ethanol withdrawal significantly suppressed the ethanol-induced rewarding effect. Our findings suggest that the increase in PP2A caused the dephospholylation of HDAC5, resulting in the increase of HDAC5 nuclear transport in ethanol relapse.
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Free Research Field |
神経科学・薬理学
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