The validity of the reinstatement model of craving and relapse to drug use
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The reinstatement procedure has been used increasingly as a laboratory model of craving and relapse to drug abuse. With the number of reports involving this procedure growing, its validity as a model of relapse merits discussion.
The present commentary addresses the validity of the reinstatement procedure in relation to the following three types of models: 1) formal equivalence models, which are assessed on the basis of how well they resemble some phenomenon outside the laboratory (i.e. face validity); 2) correlational models, which are assessed on the basis of how well they predict outcomes of various interventions (such as drug administration or environmental change) when effected outside the laboratory (i.e. predictive validity); and 3) functional equivalence models, which are assessed on the basis of whether the laboratory phenomenon is mechanistically identical or reasonably similar to the phenomenon outside the laboratory (i.e. content validity).
In order to evaluate the reinstatement model, we briefly examined its various forms and uses, and compared preclinical outcomes to what is known about relapse from the clinical literature.
In its most general form, the reinstatement model has reasonable face validity; that is, there is a general agreement in appearance or form of the behavior in the model and the clinical target, relapse. This face validity is generally absent for the procedure when it is used as a model of craving. The predictive validity of the model has not been established. Evidence from studies of treatments for drug relapse have not supported the validity of the model, however from studies of the effects of the presentation of various types of stimuli (e.g. drug "priming") there is mixed evidence supporting predictive validity. With regard to functional equivalence, there is reasonable evidence supporting functional commonalities between drug self-administration in laboratory animals and human drug abusers, which lends support to the validity of the reinstatement model. However, there are several specific areas of departure between the methods and results using the model and clinical practices and observations about relapse, suggesting a lack of functional equivalence.
There is reasonable evidence to support the face validity of the model, but at this time, neither its predictive validity nor functional equivalence has been fully established, which underscores the need for caution in generalizing results from the model to the clinical condition.
KeywordsReinstatement Animal models Drug craving Relapse to drug abuse Model validation
The preparation of this paper was supported by grants from the National Institute on Drug Abuse RO1DA09378 and RO1DA08076 (S.T. Higgins, Principle Investigator), as well as funding by the National Institute on Drug Abuse Intramural Research Program (J.L. Katz, Principle Investigator). J.L.K. thanks Dr. Barry Hoffer for his support. We also thank Dr. Alice Young for comments on an earlier version of the manuscript, Drs. Klaus Miczek and S.S. Negus for stimulating discussions, and Drs. Miczek and Yavin Shaham for inviting our participation in this project.
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