Abstract
Drug addiction is a leading cause of disability worldwide, with more than 70,000 Americans dying from drug overdose in 2019 alone. While only a small percentage of chronic drug users escalate to drug addiction, little is understood on the precise mechanisms of this susceptibility. Early life adversity is causally relevant to adult psychiatric disease and may contribute to the risk of addiction. Here we review recent pre-clinical evidence showing that early life exposure to stress and/or drugs regulates changes in behavior, gene expression, and the epigenome that persist into adulthood. We summarize the major findings and gaps in the preclinical literature, highlighting studies that demonstrate the often profound differences between female and male subjects.