In humans, exposure to early life stress (ELS) is an established risk factor for the development of substance use disorders (SUDs) during later life. Similarly, rodents exposed to ELS involving disrupted mother-infant interactions, such as maternal separation (MS) or adverse caregiving due to scarcity-adversity induced by limited bedding and nesting (LBN) conditions, also exhibit long-term alterations in alcohol and drug consumption. In both humans and rodents, there is a range of addiction-related behaviors that are associated with drug use and even predictive of subsequent SUDs. In rodents, these include increased anxiety-like behavior, impulsivity, and novelty-seeking, altered alcohol and drug intake patterns, as well as disrupted reward-related processes involving consummatory and social behaviors. Importantly, the expression of these behaviors often varies throughout the lifespan. Moreover, preclinical studies suggest that sex differences play a role in how exposure to ELS impacts reward and addiction-related phenotypes as well as underlying brain reward circuitry. Here, addiction-relevant behavioral outcomes and mesolimbic dopamine (DA) dysfunction resulting from ELS in the form of MS and LBN are discussed with a focus on age- and sex-dependent effects. Overall, these findings suggest that ELS may increase susceptibility for later life drug use and SUDs by interfering with the normal maturation of reward-related brain and behavioral function.
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