1998 Fiscal Year Final Research Report Summary
Ethanol Sensitivity of Fyn-deficient mice
| Project/Area Number |
09410023
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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 |
実験系心理学
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| Research Institution | The Institute of Physical and Chemical Research (RIKEN) |
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Principal Investigator |
NIKI Hiroaki RIKEN,Brain, Science Institute, Lab.for Neurobiology of Emotion, Lab.Head, 情報機構研究チーム, チームリーダー(研究職) (10073074)
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| Co-Investigator(Kenkyū-buntansha) |
YAGI Takeshi Institute of Physiological Sciences, Lab.of Neurobiol.& Behav.Genetics, Associat, 生理学研究所・高次神経機構, 助教授 (10241241)
MIYAKAWA Tsuyoshi RIKEN,Brain, Science Institute, Lab.for Neurobiology of Emotion, Scientist, 情報機構研究チーム, 研究員 (10301780)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Fyn-tyrosine kinase / Ethanol sensitivity / Mutant mice / NMDA receptor / Rightin reflex / Tyrosine phosphorylation / Gene targeting / Western blotting |
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| Research Abstract |
Animals vary in their sensitivity to ethanol (EtOH), a trait at least partly determined by genetic factors. To identify possible responsible genes, mice lacking Fyn, a non-receptor type tyrosine kinase, were investigated. Fyn-deficient mice were hypersensitive to the hypnotic effect of EtOH as measured by the duration of loss of righting reflex. The hypersensitivity is specific to EtOH since no significant differences were found in the duration of loss of righting reflex induced by flurazepam (a benzodiazepine derivative). Analysis of the blood EtOH concentration revealed no differences between Fyn-deficient and control mice. Thus, lack of Fyn tyrosine kinase exacerbates the hypnotic effects of EtOH.
The administration of EtOH enhanced tyrosine phosphorylation of the NMDA receptor (NMDAR) in the hippocampus of control mice, but not of Fyn deficient mice.
The inhibition of NMDAR-mediated EPSPs by EtOH is known to be gradually reduced during EtOH exposure in slice experiment (acute tolerance). Acute tolerance to EtOH inhibition of NMDAR-mediated EPSPs in hippocampal slices developed in control mice, but not in Fyn-deficient mice. These results indicate that Fyn affects behavioral, biochemical, and physiological responses to EtOH.
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