Conditioned stimuli associated with cocaine

The present series of experiments tested the ability of conditioned stimuli associated with cocaine to influence behavior, using rodent models of addiction. Experiments 1 and 2 tested the hypothesis that cocaine cues become extra strong conditioned reinforcers compared to cues paired with non-drug reinforcers. In Experiment 1, rats were trained to lever press for intravenous cocaine infusions and grain pellets. The two reinforcers were paired with distinct audiovisual cues. When allowed to choose between these alternatives, rats chose grain on ~70-80% of trials. However, after extinguishing lever pressing, reintroduction of press-contingent cues during a test for cue-induced reinstatement generated more cocaine seeking than grain seeking. This effect was also observed on 3- and 8-week follow up tests. To examine whether the same pattern of results would occur with two non-drug reinforcers, Experiment 2 replicated Experiment 1 using grain and sucrose as reinforcement alternatives. Rats chose sucrose over grain on ~70-80% of choice trials. In contrast to the results of Experiment 1, the cue associated with the preferred reinforcer -- i.e., sucrose -- produced greater responding than the cue paired with the non-preferred reinforcer on the reinstatement test. The disconnect between primary and conditioned reinforcement in Experiment 1 but not Experiment 2, suggests that drug cues may become exceptionally strong motivators of drug-seeking. This finding is consistent with cue-focused theories of addiction. Experiment 3 investigated the ability of a cocaine cue to influence the choice of cocaine over a grain alternative. A secondary aim was to determine whether the tendency to sign-track to a food cue predicted rats' choice of cocaine over food. First, rats were trained on a procedure where insertion of a retractable lever was paired with food. A sub-group of rats -- sign-trackers -- primarily approached and contacted the lever, while another sub-group -- goal-trackers -- approached the site of food delivery. Rats were then trained on the same choice task used in Experiment 1, where they could choose between cocaine and grain. Finally, the ability of cues previously associated with cocaine and food to influence choice behavior was investigated. No evidence was found to suggest cocaine or food cues could alter preference between cocaine and grain. Sign-trackers chose cocaine over food significantly more often than did goal-trackers. This finding adds to a growing number of studies indicating that sign-tracking may be a biobehavioral marker for an addiction-prone phenotype. In general, this series of experiments provides support for cue-focused theories of addiction and provides novel information which may offer insight into the mechanisms by which cues perpetuate drug-seeking behavior in addiction.