Yoked delivery of cocaine is aversive and protects against the motivation for drug in rats.

In Experiment 1, water-deprived rats had 5-min access to saccharin followed by active or yoked intravenous delivery of saline or cocaine (0.33 mg/infusion). Both cocaine groups avoided intake of the saccharin cue following saccharin-cocaine pairings; however, the rats in the yoked condition exhibited greater avoidance of the taste cue than did the actively administering rats. Experiment 2 evaluated subsequent self-administration behavior on fixed- and progressive-ratio schedules of reinforcement. The results showed that prior yoked exposure to cocaine reduced subsequent drug-taking behavior on a progressive-ratio but not on a fixed-ratio schedule. Finally, Experiment 3 used a choice test to determine the impact of yoked drug delivery on the relative preference for cocaine versus water. The results showed that rats with a history of self-administering cocaine preferred to perform operant behaviors on the side of the chamber previously paired with cocaine, whereas the rats with a history of yoked delivery of cocaine avoided this side. These data show that, in most rats, the unpredictable, uncontrollable delivery of cocaine protects against the subsequent motivation for cocaine through an aversive mechanism.