Fyn-Kinase as a Determinant of Ethanol Sensitivity: Relation to NMDA-Receptor Function

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Science  24 Oct 1997:
Vol. 278, Issue 5338, pp. 698-701
DOI: 10.1126/science.278.5338.698

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Animals vary in their sensitivity to ethanol, a trait at least partly determined by genetic factors. In order to identify possible responsible genes, mice lacking Fyn, a non–receptor type tyrosine kinase, were investigated. These mice were hypersensitive to the hypnotic effect of ethanol. The administration of ethanol enhanced tyrosine phosphorylation of theN-methyl-d-aspartate receptor (NMDAR) in the hippocampus of control mice but not in Fyn-deficient mice. An acute tolerance to ethanol inhibition of NMDAR-mediated excitatory postsynaptic potentials 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 ethanol.

  • * These authors equally contributed to the biochemical findings.

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