Stress, depression, and anhedonia: caveats concerning animal models

Numerous animal models of depression have been advanced, each having multiple attributes and some limitations. This review provides caveats concerning etiologically valid animal models of depression, focusing on characteristics of the depressive subtype being examined (e.g. typical vs atypical major depression, dysthymia, melancholia), and factors that contribute to the interindividual behavioral variability frequently evident in stressor-related behavioral paradigms. These include the stressor type (processive vs systemic stressors), and characteristics of the stressor (controllability, predictability, ambiguity, chronicity, intermittence), as well as organismic variables (genetic, age, sex), experiential variables (stressor history, early life events) and psychosocial and personality factors that moderate stressor reactivity. Finally, a model of depression is reviewed that evaluates the effects of stressors on hedonic processes, reflected by responding for rewarding brain stimulation. Anhedonia is a fundamental feature of depression, and assessment of stressor-related reductions in the rewarding value of brain stimulation, especially when coupled with other potential symptoms of depression, provides considerable face, construct and predictive validity. Stressful events markedly impact rewarding brain stimulation, and this effect varies across strains of mice differentially reactive to stressors, is modifiable by antidepressant treatments, and allows for analyses of the contribution of different brain regions to anhedonic processes. The paradigm is sensitive to several factors known to acts as moderators of stress responses, but analyses remain to be conducted with regard to several such variables.