Also the understanding of antideprcssantinduced processes has greatly increased in the past years (eg, ref 30). A summary of animal models of depression that are classified according to type and sensitivity to chronic drug treatment is presented in Table /.According to Willner and Mitchell,31 the diathesis models summarize those paradigms that involve a genetically determined PD98059 manufacturer predisposition for the depressive illness, whereas in mere stress models external stimuli are the only factors triggering changes in behavior and physiology. Social dominance models are those that use natural (social) stressors and arc considered as a subset of the stress Inhibitors,research,lifescience,medical models. Table I. Animal models

of depression. Many of the paradigms Inhibitors,research,lifescience,medical addressed above are more correctly described as models of stress rather than models of depression. Not all responses to stress are maladaptive, because the stress response may also fulfill adaptive or protective functions. Therefore, to truly model depression, other factors such as the genetic background that might cause a predisposition for the disease must also be taken into consideration. However, studies looking at stressful Inhibitors,research,lifescience,medical early life experiences and the type of stressresponsiveness later in life highlight a key area. They may help to understand the processes that in conjunction with environmental stress can lead to depression in some individuals but

Inhibitors,research,lifescience,medical not in others. With the emergence of specific genetic factors more defined models may be created in the near future. In the case of major depressive illness, we know that genetic factors can only account for about 30% of the variance, and environmental factors clearly play a major role in inducing the illness.32 However, the development of models of depression based on the interaction between stress and genetic vulnerability appears plausible. Generation of specific strains or lines of rats or mice

may be advantageous. Studies in knockout models with a mutation in a single gene Inhibitors,research,lifescience,medical may be of limited usefulness because of confounding factors such as developmental adaptational processes. Conditional knockouts may be considered as an improvement, but they also can inform us only about the role of a single gene. Therefore, the more complex models involving the interaction of genes and environment could supposedly yield more useful information. Validity of animal models The importance SB-3CT of chronic drug treatment Pharmacological tests and models sensitive to acute drug treatment are not included in this overview. These models, perhaps more appropriately called “screens,” 33 have been designed to detect most existing antidepressants. The mechanism(s) of action by which test compounds produce positive results in such screens may not be identical, or even not similar to the mechanisms underlying their clinical effects.