Over-expression of the fyn-kinase gene reduces hypnotic sensitivity to ethanol in mice.

Our previous work indicated a role for fyn-kinase in mediating several ethanol- and GABA(A) agonist-mediated behaviors. In the present work we investigate behavioral sensitivity to ethanol and several GABA(A) compounds in mice that over-express fyn-kinase in forebrain to further characterize the role of this non-receptor tyrosine kinase in the mediation of ethanol sensitivity. Transgenic mice over-expressing fyn-kinase were tested for sensitivity to ethanol-induced loss of righting reflex and ethanol preference drinking using a two-bottle choice drinking paradigm.

Deletion of the fyn-kinase gene alters sensitivity to GABAergic drugs: dependence on beta2/beta3 GABAA receptor subunits.

Tyrosine phosphorylation can modulate GABA(A) receptor function, and deletion of the fyn-kinase gene alters GABAergic function in olfactory bulb neurons, as reported by Kitazawa, Yagi, Miyakawa, Niki, and Kawai (J Neurophysiol 1998;79:137-142). Our goal was to determine whether fyn gene deletion altered behavioral and functional actions of compounds that act on GABA(A) receptors. Such evidence might suggest a role for fyn-kinase in modulating GABA(A) receptor function, possibly via direct interactions between the kinase and receptor.

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.