title: The reinstatement model of drug relapse: history, methodology and major findings.
abstract: OBJECTIVE
  The reinstatement model is currently used in many laboratories to investigate mechanisms underlying relapse to drug seeking. Here, we review briefly the history of the model and describe the different procedures that have been used to study the phenomenon of reinstatement of drug seeking. The results from studies using pharmacological and neuroanatomical techniques to determine the neuronal events that mediate reinstatement of heroin, cocaine and alcohol seeking by acute priming injections of drugs, drug-associated cues and environmental stressors are summarized. In addition, several issues are discussed, including (1) the concordance between the neuronal mechanisms involved in drug-induced reinstatement and those involved in drug reward and discrimination, (2) the role of drug withdrawal states and periods in reinstatement of drug seeking, (3) the role of neuronal adaptations induced by exposure to drugs in relapse, and (4) the degree to which the rat reinstatement model provides a suitable preclinical model of relapse to drug taking.
  
  
  CONCLUSIONS
  The data derived from studies using the reinstatement model suggest that the neuronal events that mediate drug-, cue- and stress-induced reinstatement of drug seeking are not identical, that the mechanisms underlying drug-induced reinstatement are to some degree different from those mediating drug discrimination or reward, and that the duration of the withdrawal period following cocaine and heroin self-administration has a profound effect on reinstatement induced by drug cues and stress. Finally, there appears to be a good correspondence between the events that induce reinstatement in laboratory animals and those that provoke relapse in humans.
authors.affiliation: Behavioral Neuroscience Branch, NIDA/IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, USA. yshaham@intra.nida.nih.gov.
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
authors.affiliation: Behavioral Neuroscience Branch, NIDA/IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, USA.
authors.forename: Uri
authors.initials: U
authors.lastname: Shalev
authors.affiliation: Behavioral Neuroscience Branch, NIDA/IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Psychiatry, University of Chicago, Chicago, Ill., USA, USA.
authors.forename: Harriet
authors.initials: H
authors.lastname: de Wit
authors.affiliation: Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec, Canada, Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Stewart
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control* / Q000523:psychology*; D003463:Cues; D006801:Humans; D008960:Models, Psychological; D055502:Secondary Prevention; D013997:Time Factors