Abstract
BACKGROUND: The persistent threat of the opioid epidemic warrants investigation into risk factors that predispose individuals to opioid use disorder (OUD). Adolescent stress has been linked to enhanced risk for OUD in humans, however attempts to model this preclinically have yielded mixed results. Additionally, few studies have explored whether adolescent stress modulates the reinforcing effects of prescription opioids. Here we investigate the impact of acute adolescent stress on oxycodone self-administration in male and female rats. METHODS: Adolescent male and female rats underwent acute restraint stress during concurrent exposure to predator odor, or control handling. Approximately one week later, subjects were allowed to acquire IV oxycodone self-administration (0.03 mg/kg/inf) over 10 sessions (2 h/day) under a fixed-ratio 1 (FR1) schedule of reinforcement. Following three additional FR1 sessions and seven sessions under FR3, rats underwent two progressive-ratio tests (0.03 mg/kg/inf and 0.06 mg/kg/inf, respectively). Separate groups of adolescent rats underwent similar experimental manipulations but were trained on sucrose reinforcement. RESULTS: Adolescent stress did not affect the rate of acquisition of IV oxycodone self-administration. However, oxycodone self-administration escalated during post-acquisition FR1 sessions and remained elevated during FR3 sessions in stressed rats as compared to unstressed controls. Adolescent stress exposure did not affect responding during progressive-ratio tests, nor did it affect any measure of sucrose pellet reinforcement. CONCLUSIONS: The present results are the first to demonstrate adolescent stress-induced enhancement of oxycodone reinforcement in rats and provide a preclinical model for investigating the neurobiological mechanisms by which adolescent stress increases vulnerability for prescription opioid misuse.