Alterations of the POMC-promoter-methylation and its derivative alpha-MSH in a rodent model for alcohol dependence

Abstract

Introduction Till this day the molecular mechanisms underlying alcohol dependence are far from being understood in its entirety. Repeatedly the HPA-axis got in the focus of research for alcohol dependence. Many of these works show an association between alcohol dependence and the answer of the HPA-axis on its different levels. POMC and its derivative alpha-MSH as part of the HPA-axis are supposed to mediate alcohol craving. To investigate the role of alpha-MSH for craving we used a rodent model for alcohol dependence. Methods To prove our hypothesis we used a rodent model with 90 male wistar-rats which were housed individually in single cages. Water, 3 alcohol-solutions (5%, 10% and 20%) and food were offered to the animals ad libitum for one year (4 bottle paradigm), whereas control groups got 4 bottles filled with water. The continuous alcohol consumption of the animals was interrupted by scheduled alcohol-deprivation-phases. During the animal trial a manifest alcohol dependence was induced. The blood and tissues, obtained at the end of the trial, were analysed using direct bisulfite-sequencing (methylation status) and Elisa (alpha-MSH protein levels). Results and discussion The group of alcohol dependent animals showed an altered methylations status of the POMC-gene-promoter and altered levels of alpha-MSH compared to the control group. These findings are in line with our previous results showing a significant correlation between symptoms of alcohol craving and POMC-promoter methylation. These new data confirm our results from humane materials and clarify the meaning of alpha-MSH for craving in alcohol dependence.