Effect of Chronic Administration of Ethanol on the Regulation of Tyrosine Kinase Phosphorylation of the GABAA Receptor Subunits in the Rat Brain

摘要

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 GABAA receptor subunits in rat brain regions. In the present study, we investigated the regulation of the tyrosine kinase phosphorylation of the GABAA receptor α1-, β2- and γ2-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 α1 subunit, whereas there was an up-regulation or no change in the case of β2- and γ2-subunits of the GABAA 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 GABAA receptors may play a significant role in ethanol dependence.