Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats.

Early life stress (ELS) or alcohol consumption can influence DNA methylation and affect gene expression. Monoamine oxidase A (Maoa) encodes the enzyme that metabolizes monoaminergic neurotransmitters crucial for the stress response, alcohol reward, and reinforcement. Previously, we reported lower Maoa expression in the nucleus accumbens and dorsal striatum of male rats exposed to ELS during the first three postnatal weeks, and to voluntary alcohol consumption in adulthood, compared with controls. The present study continued to investigate the effect of ELS and alcohol consumption on Maoa methylation, and its relation to Maoa expression in these animals. We selected candidate CpGs after performing next-generation bisulfite sequencing of the Maoa promoter, intron 1-5, and exons 5 and 6, together composed of 107 CpGs (5'-cytosine-phosphate-guanosine-3'), in a subgroup of rats. Pyrosequencing was used to analyze the methylation of 10 candidate CpGs in the promoter and intron 1 in the entire sample. ELS and alcohol displayed an interactive effect on CpG-specific methylation in the dorsal striatum. CpG-specific methylation correlated with Maoa expression, corticosterone levels, and alcohol consumption in a brain region-specific manner. CpG-specific methylation in the Maoa promoter was a potential moderator of the interaction of ELS with alcohol consumption on Maoa expression in the NAc. However, the findings were sparse, did not survive correction for multiple testing, and the magnitude of differences in methylation levels was small. In conclusion, CpG-specific Maoa methylation in the promoter and intron 1 may associate with ELS, alcohol consumption, and Maoa expression in reward-related brain regions.