Animal models of depression: an overview.

Although animal models cannot replicate human psychopathology in every detail, they should properly be conceived as experimental systems in which selected and specific questions can be investigated in ways impossible to do in humans. In considering the general kinds of animal models, distinctions must be drawn among those designed to simulate specific signs or symptoms, those designed to test a specific etiological theory, those designed to study underlying behavioral and neurobiological mechanisms, and those whose principal purpose is to permit pre-clinical drug evaluation. If, for example, drug evaluation is the first concern, the empirical validity of the model in predicting the therapeutic efficacy of drugs is primary, whereas the mechanisms responsible for inducing the syndrome, and behavioral similarity issues become secondary. The available models of depression are reviewed in the light of their specific advantages and limitations, including those induced pharmacologically, maternal and peer separation, learned helplessness, chronic stress, changes in dominance hierarchy, intra-cranial self-stimulation, conditioned motionlessness and behavioral despair models. Since multiple variables are involved in the etiology of depressions, animal models offer the possibility of evaluating their main effects and interactions in a controlled prospective manner. While caution is required in cross-species reasoning, there are nevertheless guidelines, and the continuing development of a comparative approach in Psychiatry has great potential.