Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes
Abstract
Significance Opioid use disorder is on the rise, as are efforts to understand vulnerability to misuse. However, understanding resilience to drug abuse is also critical to the development of novel treatments. Here we demonstrate that a brief postnatal exposure to a low-resource environment—using the limited bedding and nesting (LBN) manipulation—promoted resilience to addiction-related phenotypes in adult male rats. Specifically, LBN reduced impulsivity, morphine self-administration, and nucleus accumbens (NAc) glutamate transmission in males, effects not seen in females. By comparing the sexes, we found that changes in NAc gene transcription unique to LBN males may contribute to resilience. Importantly, these molecular changes reveal new targets that could guide the development of pharmacotherapies for opioid use disorder. Experiencing some early life adversity can have an “inoculating” effect that promotes resilience in adulthood. However, the mechanisms underlying stress inoculation are unknown, and animal models are lacking. Here we used the limited bedding and nesting (LBN) model of adversity to evaluate stress inoculation of addiction-related phenotypes. In LBN, pups from postnatal days 2 to 9 and their dams were exposed to a low-resource environment. In adulthood, they were tested for addiction-like phenotypes and compared to rats raised in standard housing conditions. High levels of impulsivity are associated with substance abuse, but in males, LBN reduced impulsive…
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