Deletion of the fyn-kinase gene alters behavioral sensitivity to ethanol.
BACKGROUND
An earlier study showed that deletion of the fyn-kinase gene enhanced sensitivity to ethanol's sedative hypnotic effects and suggested that this was associated with diminished fyn-kinase phosphorylation of NMDA receptors. The authors of that study speculated that this resulted in an inability of the null mutants to develop acute tolerance to ethanol, leading to the longer ethanol-induced sleep times. However, in vivo acute tolerance to ethanol was not examined directly.


METHODS
To address the role of fyn-kinase in mediating acute tolerance, as well as sensitivity to several other behavioral effects of ethanol, we studied an independently generated population of fyn null mutant and wild-type mice.


RESULTS
Homozygous mutants exhibited longer ethanol sleep times that could not be attributed to differences in initial sensitivity, and impaired acute tolerance to the motor incoordinating effects of ethanol as measured by using the stationary dowel, but not the rotarod. Fyn-kinase null mutants were more sensitive to the anxiolytic effects of ethanol when tested using the elevated plus maze, and males displayed a lower preference for ethanol in a two-bottle choice paradigm. Finally, mutant and wild-type mice did not differ in sensitivity to the hypothermic effects of ethanol. The genotypes also did not differ in blood-ethanol clearance, eliminating a metabolic explanation for these behavioral differences.


CONCLUSIONS
These results show that fyn-kinase modulates acute tolerance to ethanol and suggest a role for fyn in mediating ethanol's anxiolytic and reinforcing properties.
Boehm
Stephen L
SL
Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Texas 78712-0159, USA. slboehm@mail.utexas.edu
Peden
Laura
L
Chang
Rose
R
Harris
R Adron
RA
Blednov
Yuri A
YA
D000818:Animals; D016739:Behavior, Addictive / Q000201:enzymology* / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics*; D019061:src-Family Kinases
D009363:Neoplasm Proteins; D000431:Ethanol; D011505:Protein-Tyrosine Kinases; C490512:Frk protein, mouse; D019061:src-Family Kinases