Animal models of depression: A lesson from the pharmacologic sensitivity of antidepressant drugs and candidates

Abstract

There are many studies on the effects of antidepressants in normal animals, but a more relevant study is to evaluate the effects of the drugs in paradigms designed to mimic symptoms of human depression. Animal models of repeated stress exposure simulate the presumed etiology of depression, and this stress may be produced by exogenous corticosterone administration. Additionally, rodents reared in isolation from early life have marked behavioral differences from socially reared animals. Despair is a common symptom of depression, and the forced swim and tail suspension tests are widely used to measure this behavior in rodents. Anhedonia, or markedly diminished interest or pleasure, is also a characteristic feature of depression, and tests that assess this behavior are important for studying the etiology of depression. Thus, we have developed a novel and simple method, which we have termed the female encounter test, for assessing motivation in adult mice. We have recently investigated the pharmacological action of (R)-ketamine, (S)-ketamine, and their metabolites in mouse models of depression. However, our and other studies on antidepressant-like effects of some ketamine metabolites show inconsistent results. In this symposium, we would like to discuss about what we are looking for in animal models of depression.