Challenges for translational psychopharmacology research - some basic principles

We introduce below several principles that recur in the discussion of translating preclinical findings to clinical applications, and conversely, developing animal models of human disorders: 1. The translation of preclinical data to clinical concerns is more successful when the scope of experimental models is restricted to a core symptom of a psychiatric disorder. 2. Preclinical experimental models gain in clinical relevance if they incorporate conditions that induce maladaptive behavioral or physiological changes that have some correspondence with species-normative behavioral adaptations. 3. Preclinical data are more readily translated to the clinical situation when they are based on converging evidence from several experimental procedures, each capturing cardinal features of the disorder. 4. The more closely a model approximates significant clinical symptoms, the more likely it is to generate data that will yield clinical benefits. 5. The choice of environmental, genetic, and/or physiological manipulations that induce a cardinal symptom or cluster of behavioral symptoms reveals the theoretical approach used to construct the model. 6. Preclinical experimental preparations that are validated by predicting treatment success with a prototypic agent are only able to detect alternative treatments that are based on the same mechanism as the existing treatment that was used to validate the screen. 7. The degree to which an experimental model fulfills the criteria of high construct validity relative to face or predictive validity depends on the purpose of the model. 8. Psychological processes pertinent to affect and cognition can only be studied in preclinical models if they are defined in behavioral and neural terms.