The Effects of Early Life Stress On Impulsive and Risky Decision-Making Behaviors

Abstract

Early life stress is a prevalent problem affecting many worldwide and can be experienced in a variety of ways, including limited access to resources as in many low socioeconomic status households. In humans, exposure to stress early in life is linked to various psychiatric conditions such as substance use disorder, attention-deficit/hyperactivity disorder, and gambling. One characteristic that these disorders share is elevated impulsivity. Impulsivity is a multifaceted construct and often behaviors are classified as either an impulsive choice (e.g., inability to delay gratification) or an impulsive action (e.g., inability to inhibit premature responses). In the first set of experiments presented here, we characterize the limited bedding and nesting model (LBN) of early life adversity in rodents, in which rat dams and their pups are housed in a limited resource environment from postnatal day (PND) 2 through 9. This model works by inducing stress in the dams, which alters their maternal care behaviors towards pups. As a result, this altered care can be stressful for the developing pups. We have found that LBN exposure promoted resilience to addiction-related phenotypes in adult male, but not female rats. Specifically, LBN reduced impulsive choice, morphine self-administration, and nucleus accumbens (NAc) glutamate transmission in males, effects not seen in females. Additionally, changes in NAc gene transcription unique to LBN males may contribute to resilience. We build on these findings in the second set of experiments, which explores whether LBN alters impulsive action, risky decision-making, and the gene transcriptome of the orbitofrontal cortex (OFC). We found that LBN increased impulsive action in males. Additionally, we found LBN exposure in rats across sex reduces risky choice. These changes in behavior were accompanied by highly specific changes in gene transcription in the OFC, which is a brain region that mediates both impulsive and risky decision-making behaviors. The identification of genes and signaling pathways that are altered by LBN in the male OFC lays the groundwork for future studies investigating the mechanisms by which early life stress alters addiction-related phenotypes.