Role of Fyn tyrosine kinase in ethanol consumption by mice

Background: Mice deficient for the intracellular protein Fyn tyrosine kinase (fyn(Z)/fyn(Z) mice) have been reported to show increased alcohol sensitivity and lack of tolerance to the effects of ethanol. To further study the involvement of Fyn in neurobehavioral effects of alcohol, we examined ethanol consumption and relapse drinking behavior in fyn(Z)/fyn(Z) mice. Methods: Fyn(Z)/fyn(Z) and wild-type mice were given a free choice between water and increasing concentrations of ethanol (2-16%). Once a stable baseline of 16% ethanol consumption was established, access to. ethanol was withdrawn for 2 weeks and then reinstated, to measure the alcohol deprivation effect (ADE). Forced swim stress was performed thereafter on 2 consecutive days. In a final experiment we studied alcohol sensitivity by measuring ethanol-induced loss of righting reflex (LORR). Results: The concentration of available ethanol had a significant effect on ethanol consumption and preference; however, there was no significant effect of genotype on these measures. Deprivation from ethanol led to a significant increase in ethanol consumption by all mice with no significant impact of genotype on ethanol consumption or water consumption during the ADE. Two consecutive days of forced swim stress led to a significant increase in ethanol consumption; again however, genotype had no effect on stress-associated ethanol consumption. Surprisingly, however, Fyn(Z)/fyn(Z) mice showed no differences in alcohol sensitivity when compared to wild-type animals, in contract to previously reported results (Miyakawa et al., 1997). Conclusions: Deletion of the Fyn tyrosine kinase gene may be involved in ethanol sensitivity but this effect may depend on a gene-environment interaction. Fyn does not influence ethanol consumption, neither under basal conditions nor following a deprivation period or stress. This finding indicates that phosphorylation and activation of N-methyl-D-aspartate (NMDA) receptors through Fyn is not a critical mechanism in alcohol drinking or relapse behavior.