Neuroepigenetic consequences of adolescent ethanol exposure.

ABSTRACT

Adolescence is a critical developmental period characterized by ongoing brain maturation processes including myelination and synaptic pruning. Adolescents experience heightened reward sensitivity, sensation seeking, impulsivity, and diminished inhibitory self-control, which contribute to increased participation in risky behaviors, including the initiation of alcohol use. Ethanol exposure in adolescence alters memory and cognition, anxiety-like behavior, and ethanol sensitivity as well as brain myelination and dendritic spine morphology, with effects lasting into adulthood. Emerging evidence suggests that epigenetic modifications may explain these lasting effects. Focusing on the amygdala, prefrontal cortex and hippocampus, we review studies investigating the epigenetic consequences of adolescent ethanol exposure. Ethanol metabolism globally increases donor substrates for histone acetylation and histone and DNA methylation, and this chapter discusses how this can further impact epigenetic programming of the adolescent brain. Elucidation of the mechanisms through which ethanol can alter the epigenetic code at specific transcripts may provide therapeutic targets for intervention.