Challenges for translational psychopharmacology research—some basic principles

Abstract

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.

Chronic administration of atypical antipsychotics improves behavioral and synaptic defects of STOP null mice

“…These results indicate that LTP measurements in STOP null mice may discriminate between APs with or without glutamatergic profiles. A translational preclinical model of human psychiatric disorder is all the more relevant that it respects construct, face, and predictive validity (Ellenbroek and Cools 1990;Miczek and de Wit 2008). As outlined in the introduction, STOP null mouse model fulfils the construct and face validity: It is constructed from the neurodevelopmental hypothesis of schizophrenia, with synaptic impairment.…”

Effects of chronic fluoxetine treatment on anxious behaviour of BALB/c mice in a 3-dimensional maze

“…The above conflicting results were mostly obtained in unconditioned tests of anxiety, which have been reported to produce inconsistent results with a wide range of psychoactive compounds (Andrews et al, 2014;Cryan & Sweeney, 2011;Griebel & Holmes, 2013;Miczek & de Wit, 2008;Rodgers et al, 1995Rodgers et al, , 2002; Thompson et al, 2015). One of the major limitations of these tests is that they cannot be used for more Correspondence: Dr. A. Ennaceur, Sunderland Pharmacy School, University of Sunderland, Wharncliffe Street, Sunderland, SR1 3SD, UK.…”

Nonhuman primate models of social behavior and cocaine abuse

“…The neurobiology of aggression and the interactions between genetics and social behavior have great relevance to understanding human behavior (Miczek et al 1984, 2004; Miczek and de Wit 2008; Miczek and de Almeida 2012; Takahashi et al 2012). Recent studies have extended the pioneering studies of Miczek, Crowley and colleagues examining drug effects on social behavior to incorporate cocaine self-administration (as opposed to experimenter-administered drug administration).…”