Effects of naloxone subcutaneous pellets on relapse to morphine self-administration in post-addict rats

Female Sprague-Dawley rats were prepared with chronic cortical and muscle electrodes and i.v. cannulae. They were administered morphine by i.v. injections, then trained to lever press for i.v. self-injections of morphine (10 mg/kg) to maintain dependence, and subsequently withdrawn for two weeks. At this point, one or two pellets of naloxone base (100 mg) or placebo pellets were implanted subcutaneously. The rats were then returned to the experimental cages and allowed to self-administer morphine or isotonic saline. Rats that were implanted with two 100 mg naloxone pellets did not relapse to morphine self-injections. Although some of the rats implanted with one 100 mg pellet also failed to relapse to morphine, the remainder increased their lever pressing and morphine intake sufficiently to overcome the antagonist effect of naloxone and to reestablish dependence. Rats implanted with placebo pellets and given access to morphine reestablished lever pressing, while those given access to isotonic saline extinguished their lever pressing. These findings demonstrate the ability of the narcotic antagonist, naloxone, to suppress relapse to morphine in post-addict rats.