The main animal models of relapse are reinstatement paradigms that model the ability of re-exposure to environmental stimuli (48) or drugs (49–51) to induce drug-seeking after a period of abstinence. Relapse is of clear importance to the study of addiction, and the reinstatement model has been studied in rats (53, 54) and humans (55) and found to have high predictive validity (52). In this model, the animal first learns to self-administer a drug, and then the response is extinguished by discontinuing availability of the drug. Following extinction of the drug-seeking behavior, the behavior is reinstated by exposing the subject to environmental cues that have been associated with drugs (48, 53, 54, 56–58), stress (59–61) and by acute priming injection of drugs (49, 53, 54, 62).
