Cocaine‐Primed Reinstatement of Operant Behavior in Rhesus Monkeys with a Prolonged History of Cocaine Self‐Administration

The present study assessed the effects of long‐term cocaine exposure on the magnitude and persistence of cocaine‐primed reinstatement. Rhesus monkeys were trained to self‐administer cocaine on a second‐order schedule. Subsequently, animals underwent repeated extinction sessions until response rates decreased below 20% of cocaine maintained responding. After each block of extinction, animals were administered cocaine priming injections prior to the start of the experimental session, and peak response rates were taken as an index of reinstatement magnitude. Consecutive reinstatement experiments were conducted daily until response rates returned to extinction levels, and the number of sessions to this criterion was taken as an index of reinstatement persistence. Peak response rates were equivalent between repeated reinstatement studies. However, the time to reach extinction criteria across reinstatement trials decreased as self‐administration history increased. The results demonstrate robust reinstatement effects over multiple blocks of extinction but reinstatement was less persistent over time. Ongoing studies that allow animals to escalate their cocaine intake during extended self‐administration sessions will provide a better understanding of how escalating cocaine exposure affects relapse and drug seeking behavior. USPHS Grant DA016589, DA00517, and RR00165