Maternal separation stress increases alcohol preference regardless of DNA methylation and histone acetylation or methylation in the amygdala.

Abstract

Alcohol use disorder (AUD) is a condition with multifactorial causes, including biopsychosocial factors. Childhood exposure to stress may increase susceptibility to AUD in adulthood. Despite its significance, the interaction between stress and AUD remains unclear. This study investigated whether maternal separation stress (MS) would change epigenetic marker levels in mice's amygdala and whether these changes correlate with increased ethanol consumption and preference in adulthood. C57BL/6J pups in the maternal separation group were removed from their nests for 3 hours daily from postnatal day (PND) 1 to PND 14. Control animals remained under maternal care. All litters were weaned on PND 21, and on PND 60, mice were subjected to a two-bottle choice protocol using one bottle containing water and another containing ethanol in crescent concentrations (5%, 10%, 15%, and 20% w/v; every three days) for 8 hours daily. Following a 3-day withdrawal, a reinstatement test using the two-bottle choice paradigm was conducted. Afterward, the amygdala was dissected for analysis of acetylated histones, H3 dimethylated in lysine 9, Sirtuin-1, and DNA methyltransferases-1 by Western Blotting. Results demonstrated that exposure to maternal separation during childhood increased mice ethanol preference but not consumption during adulthood. We also observed no alterations in the levels of the epigenetic markers analyzed. These results support the hypothesis that maternal separation exposure can influence ethanol-related behaviors in the later phases of development.