Models of affective illness: chronic mild stress in the rat

Described in this unit is a chronic mild stress (CMS) procedure used for predicting an antidepressant response. Following exposure to a variety of mild stressors for a period of several weeks, rat behavior is modified in a number of ways. Among these is a substantial reduction in consumption of a 1% sucrose solution. Chronic administration of antidepressant drugs reverses diminished enthusiasm for sucrose in these subjects. While most antidepressants must be administered for at least 3 to 5 weeks to normalize behavior, there are treatments that display a more rapid onset of action. More recently, it has been shown that the CMS-induced deficit in sucrose consumption can also be reversed by second-generation antipsychotics. Based on these findings, the CMS model can be employed in discovery programs aimed at identifying antianhedonic drugs (e.g., antidepressants and antipsychotics) that act more quickly than existing agents.