Vol 4 n° 4 - Drug Development
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nimal  models  are  defined  as  experimental preparations developed in one species in order to study phenomena existing in another species.When addressing animal models of human psychopathology, attempts are made to reproduce in animals some syndromes or symp- toms  resembling  as  far  as  possible  some  human  syn- dromes or symptoms in order to study particular aspects of  human  psychopathology. When  utilizing  an  animal model for studying a human disease, it is important to consider the validity of such a simulation.The validity of animal models of psychiatric disorders is usually assessed by different criteria: ideally, the model should resemble the pathology it simulates in terms of its etiology, its biol- ogy, its symptomatology, and its treatment.1 Three differ- ent types of validity are usually considered: predictive validity, aspect validity, and theoretical validity. Predictive validity is determined by appropriate response of the animal model to therapeutic agents.The model must discriminate clinically efficacious agents from those which are not.The simulation should identify substances that ame- liorate, but also those that deteriorate the simulated pathol- ogy. In addition, the model must be responsive to all cate- gories of medications used to treat the simulated condition. Aspect  validity  refers  to  phenomenological  similarity between the model and the pathology being simulated. It mainly relates to symptomatology and mode of treatment. Usually, models focus on one particular symptom of a given disorder.The difficulty is to appreciate the importance of this particular symptom in the definition of the syndrome. Concerning the treatment, most psychotropic drugs need to be regularly administered over several weeks or months. Consequently, in the model, substances should continue to be efficacious after chronic administration. In addition, and similar to what happens in the clinic, we might expect a delay in the appearance of the first beneficial effects. Finally, evaluating the theoretical validity of an animal model consists in identifying the behavioral variable that will be simulated, estimating its degree of homology with the behavior in the simulation, and appreciating the mean- B a s i c   r e s e a r c h 3 5 1 Simulating the anhedonia symptom of depression in animals Jean-Luc Moreau, PhD A Keywords: anhedonia; depression; chronic mild stress; model; rat Author  affiliations:  Pharma  Division,  Preclinical  CNS  Research,  72/141,  F. Hoffmann-La Roche, CH-4070 Basel, Switzerland Address for correspondence: Dr Jean-Luc Moreau, Pharma Division, Preclinical CNS Research, 72/141, F. Hoffmann La Roche, CH-4070 Basel, Switzerland
(e-mail: jean-luc.moreau@roche.com) One of the two core symptoms of depression is anhedo- nia, the loss of interest or pleasure in daily activities. Stressful life events are recognized as predisposing factors in the etiology of depression. Rats subjected to a chronic, mild,  unpredictable  stress  regimen  exhibit  behavioral deficits consistent with a loss of responsiveness to reward, such as decreased sucrose consumption, decreased ability to associate rewards with a distinctive environment, and decreased sensitivity to rewarding electrical brain stimu- lation. Normal behavior is restored by chronic treatment with antidepressants or electroshocks. Chronically stressed animals also exhibit sleep abnormalities resembling those observed in depressed patients and recognized as bio- logical markers of depression. Thus, stress-induced anhe- donia in rats represents an original animal model of some aspects of human depression offering convergent ele- ments of biological, symptomatological, etiological, and therapeutic validity. This simulation of depression may prove useful for better understanding of the pathophys- iological mechanisms involved in depressive disorders. Dialogues Clin Neurosci. 2002;4:351-360.