Abstract
The origins and neural bases of the current opioid addiction epidemic are unclear. Genetics plays a major role in addiction vulnerability, but cannot account for the exponential recent rise in opioid abuse, so environmental factors must contribute. Individuals with history of early-life adversity (ELA) are disproportionately affected, yet whether ELA directly influences brain function to cause opioid vulnerability is unknown. We simulated ELA in female rats, which provoked a profound, selective opioid-addiction phenotype. This was characterized by resistance to extinction, increased relapse-like behavior, and, as in addicted humans, dramatic increase in economic demand. By contrast, seeking of natural rewards was unaffected. These discoveries provide novel insight into the origins and nature of reward circuit malfunction that drives opioid abuse.