LAUSR

Relapse to non‐medical use of prescription opioids often occurs after exposure to places previously associated with drug use. Here, we describe a rat model of context‐induced reinstatement of oxycodone seeking after repeated cycles of drug self‐administration and extinction‐induced abstinence. We also determined the role of mu, delta and kappa opioid receptors (MOR, DOR, KOR) in this reinstatement. We trained rats to self‐administer oxycodone for 6 h/day in context A; lever pressing was paired with a discrete cue. Next, we extinguished the lever pressing in the presence of the discrete cue in context B and then tested the rats for reinstatement of oxycodone seeking in both contexts. We retrained rats to self‐administer oxycodone in context A, re‐extinguished their lever pressing in context B and retested them for reinstatement in both contexts. Prior to testing, we injected the rats with vehicle or antagonists of MOR (naltrexone; 0.5 or 1.0 mg/kg), DOR (naltrindole; 7.5 or 15 mg/kg) or KOR (LY2456302; 5 or 10 mg/kg). We also tested the effect of naltrexone, naltrindole and LY2456302 on oxycodone self‐administration under fixed‐ratio‐1 (FR1) and progressive ratio (PR) reinforcement schedules. We observed context‐induced reinstatement of oxycodone seeking after repeated cycles of drug self‐administration and extinction. Naltrexone, but not naltrindole or LY2456302, injections decreased this reinstatement. Additionally, naltrexone increased oxycodone self‐administration under the FR1 schedule and decreased oxycodone self‐administration under the PR schedule; naltrindole and LY2456302 were ineffective. Results demonstrate a critical role of MOR, but not DOR or KOR, in context‐induced reinstatement of oxycodone seeking and oxycodone self‐administration.