Animal models for the study of antidepressant activity

Abstract

Three behavioral paradigms are presented for the study of the mechanism of action of antidepressant treatments and for the screening of new antidepressant drugs. The first model (acute escape deficit) exploits the decreased ability of a rat exposed to an unavoidable stress to avoid a noxious stimulus, and it allows us to evaluate the preventive activity of a treatment on the development of escape deficit. The second paradigm (chronic escape deficit) begins as acute escape deficit, that is then indefinitely sustained by the repeated administration of mild stressors; this model allows us to evaluate the efficacy of a treatment to revert the escape deficit. The third is a model of anhedonia based on the finding that exposure to repeated unavoidable stress prevents the acquisition of an appetitive behavior induced and maintained by a highly palatable food (vanilla sugar) in rats fed ad libitum; this paradigm assesses the efficacy of a treatment to restore an animal's motivation. A long-term (2 to 3 week) treatment with classical antidepressants, such as imipramine or fluoxetine, resulted in a clear-cut preventive and/or revertant activity in the three models.