Too many subunits so little time: Ticku's legacy on ethanol modulation of GABAA receptor subunit gene expression

Since the cloning of the many subunits of the GABAA receptor a plethora of studies were undertaken in order to understand how chronic ethanol exposure as well as ethanol withdrawal could interfere with their gene expression. Ticku’s laboratory was one of the first to study this effect of ethanol and for many years until his last publications a great effort was made to elucidate the cellular location, subunit composition and functional role of native GABAA receptors important in order to develop better drugs. More work needs to be done to understand how ethanol can interfere with the molecular mechanisms underlying the expression of the various GABAA receptor subunits and the assembly of subunit combinations to form functional receptors. In this presentation we will discuss some effects of chronic ethanol exposure and ethanol withdrawal on GABAA receptor subunit expression and related receptor function obtained by our research group using neuronal cell cultures. We will show that some changes in gene expression and function evident during ethanol withdrawal can be selectively blocked by drugs such as diazepam, flumazenil or c-hydroxybutyrate, whereas neither gaboxadol nor neuroactive steroids are effective. Moreover, some ethanol withdrawal-induced changes in gene expression seem to be steroids mediated since they can be blocked by the 5a-reductase inhibitor finasteride