Effects of acute adolescent stress on the acquisition and maintenance of intravenous oxycodone self-administration in male and female rats
Teen stress alone doesn’t start oxycodone use, but it quietly fuels later surges in intake.
01Research in Context
What this study did
Gallagher et al. (2026) stressed teenage rats for a few days.
Later they let the same rats press a lever to give themselves oxycodone.
They watched how fast the rats learned and how much drug they took over weeks.
What they found
Early stress did not change how quickly the rats learned the lever.
But after the drug was easy to get, stressed rats took more and more oxycodone.
Both male and female rats showed the same steady climb in drug use.
How this fits with other research
Rebec et al. (2005) reviewed older rat work and showed that stress lights up the prefrontal cortex, not the pleasure center, when relapse starts. Gallagher’s study adds oxycodone to that map and shows the climb starts in adolescence.
Toegel et al. (2020) and Andrade et al. (2014) found that paychecks for clean urines cut opiate use in adults. Gallagher’s rats never got a reward for skipping the drug, so intake kept rising. The two lines fit: money for abstinence works in people, while no consequence lets stress-plus-drug use run free in rats.
Davison et al. (1991) and Davison et al. (1995) gave rats morphine or cocaine under timeout schedules and saw drug-specific changes in lever pressing. Gallagher used the same IV setup but added teen stress first, extending those drug-only findings to stress-drug combos.
Why it matters
If a client says heavy use began after a rough high-school time, this rat model backs them up. It tells you stress did not "cause" the first hit, but it can quietly turn up the volume later. Build relapse plans that lower daily stress and reward drug-free behavior—exactly what the human abstinence studies did.
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02At a glance
03Original abstract
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. 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. 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. 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.
Drug and alcohol dependence, 2026 · doi:10.1016/j.drugalcdep.2026.113030