Fyn-kinase as a determinant of ethanol sensitivity: relation to NMDA-receptor function.
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.
Miyakawa
T
T
Laboratory for Neurobiology of Emotion, Brain Science Institute, RIKEN, Hirosawa, Wako-shi, Saitama-ken 351-01, Japan.
Yagi
T
T
Kitazawa
H
H
Yasuda
M
M
Kawai
N
N
Tsuboi
K
K
Niki
H
H
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005479:Flurazepam / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D011518:Proto-Oncogene Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D019000:Phosphotyrosine; D000431:Ethanol; D016202:N-Methylaspartate; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D005479:Flurazepam