Effect of chronic administration of ethanol on the regulation of tyrosine kinase phosphorylation of the GABAA receptor subunits in the rat brain.

One of the many pharmacological targets of ethanol is the GABA inhibitory system, and chronic ethanol (CE) is known to alter the polypeptide levels of the GABA(A )receptor subunits in rat brain regions. In the present study, we investigated the regulation of the tyrosine kinase phosphorylation of the GABA(A) receptor alpha(1)-, beta(2)- and gamma(2)-subunits in the rat cerebellum, cerebral cortex and hippocampus following chronic administration of ethanol to the rats. We observed either down-regulation or no change in the tyrosine kinase phosphorylation of the alpha(1) subunit, whereas there was an up-regulation or no change in the case of beta(2)- and gamma(2)-subunits of the GABA(A) receptors depending on the brain region following chronic administration of ethanol to the rats. These changes reverted back to the control level following 48 h of ethanol-withdrawal. These results suggest that tyrosine kinase phosphorylation of GABA(A )receptors may play a significant role in ethanol dependence.