Animal models of depression: pros and cons.

Animal models of depression are certainly needed but the question in the title has been raised owing to the controversies in the interpretation of the readout in a number of tests, to the perceived lack of progress in the development of novel treatments and to the expressed doubts in whether animal models can offer anything to make a true breakthrough in understanding the neurobiology of depression and producing novel drugs against depression. Herewith, it is argued that if anything is wrong with animal models, including those for depression, it is not about the principle of modelling complex human disorder in animals but in the way the tests are selected, conducted and interpreted. Further progress in the study of depression and in developing new treatments, will be supported by animal models of depression if these were more critically targeted to drug screening vs. studies of underlying neurobiology, clearly stratified to vulnerability and pathogenetic models, focused on well-defined endophenotypes and validated for each setting while bearing the existing limits to validation in mind. Animal models of depression need not to rely merely on behavioural readouts but increasingly incorporate neurobiological measures as the understanding of depression as human brain disorder advances. Further developments would be fostered by cross-fertilizinga translational approach that is bidirectional, research on humans making more use of neurobiological findings in animals.