Abstract
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 the N-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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Central Nervous System Depressants / pharmacology*
-
Ethanol / pharmacology*
-
Excitatory Postsynaptic Potentials / drug effects
-
Flurazepam / pharmacology
-
Hippocampus / metabolism
-
Hypnotics and Sedatives / pharmacology
-
In Vitro Techniques
-
Male
-
Mice
-
Mice, Knockout
-
Motor Activity / drug effects*
-
N-Methylaspartate / pharmacology
-
Phosphorylation
-
Phosphotyrosine / metabolism
-
Protein-Tyrosine Kinases / deficiency
-
Protein-Tyrosine Kinases / genetics
-
Protein-Tyrosine Kinases / metabolism*
-
Proto-Oncogene Proteins / deficiency
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / metabolism*
-
Proto-Oncogene Proteins c-fyn
-
Receptors, N-Methyl-D-Aspartate / metabolism*
Substances
-
Central Nervous System Depressants
-
Hypnotics and Sedatives
-
Proto-Oncogene Proteins
-
Receptors, N-Methyl-D-Aspartate
-
Phosphotyrosine
-
Ethanol
-
N-Methylaspartate
-
Protein-Tyrosine Kinases
-
Fyn protein, mouse
-
Proto-Oncogene Proteins c-fyn
-
Flurazepam