Early life stress and the propensity to develop addictive behaviors.

There is a vast literature on effects of early life manipulations in rodents much of which is aimed at investigating the long-term consequences related to emotion and cognition in adulthood. Less is known about how these manipulations affect responses reflective of alcohol (AUD) and substance (SUD) use disorders. The purpose of this paper is to review the literature of studies that employed early life manipulations and assessed behavioral responses to psychoactive substances, specifically alcohol, opiates, and stimulants, in rodents. While the findings with alcohol are more limited and mixed, studies with opiates and stimulants show strong support for the ability of these manipulations to enhance behavioral responsivity to these substances in line with epidemiological data. Some outcomes show sex differences. The mechanisms that influence these enduring changes may reflect epigenetic alterations. Several studies support a role for altered DNA methylation (and other epigenetic mechanisms) as biological responses to early environmental insults. The chemical changes induced by DNA methylation affect transcriptional activity of DNA and thus can have a long-term impact on the individual's phenotype. Such effects are particularly robust when they occur during sensitive periods of brain development (e.g., first postnatal weeks in rodents). We review this emerging literature as it relates to the known neurobiology of AUDs and SUDs and suggest new avenues of research. Such findings will have implications for the treatment and prevention of AUDs and SUDs and could provide insight into factors that support resiliency.