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 recent exponential rise in opioid abuse, so environmental factors must contribute. Individuals with history of early-life adversity (ELA) are disproportionately prone to opioid addiction, yet whether ELA directly influences brain development and function to cause this vulnerability is unknown. We simulated ELA in female rats, which provoked a profound opioid-addiction vulnerability. This was characterized by resistance to extinction, increased relapse-like behavior, and, as in addicted humans, major increases in opioid economic demand. By contrast, seeking of less salient natural rewards was unaffected by ELA, whereas demand for highly palatable treats was augmented. These discoveries provide novel insights into the origins and nature of reward circuit malfunction that may set the stage for addiction.
Footnotes
New data added, Figure 1 revised and Figure 2 Added, Methods updated, Introduction and Discussion revised