Table II. Similarities between main MG132 proteasome features of a depressive episode in man and chronic mild stress-induced anhedonia in rats. Data in animals are a compilation of results found in the following publications: 11, 14, 19-21, 24, and 36-40. MAO, monoamine oxidase; … Theoretical validity The stress procedure used in these studies was able to induce a decrease in sucrose consumption and/or preference, a decrease in the ability to associate pleasurable events with a particular environment,

(place preference), and an increase in the current threshold necessary Inhibitors,research,lifescience,medical to elicit, self-stimulation behavior. These results obtained by different, research groups using different strains of animals strengthen the idea that, a chronic, mild, unpredictable stress regimen induces a decreased sensitivity to pleasure, ie, an anhedonic state. Anhedonia is one of the two core symptoms of depression. Aspect validity In addition to inducing an anhedonic state, the chronic mild stress

regimen triggers Inhibitors,research,lifescience,medical the development, of several other symptoms of depression. Indeed, Inhibitors,research,lifescience,medical it is able to decrease sexual and aggressive behavior,37 inhibit locomotor activity, and induce a phase advance shift in arcadian rhythm,41 elicit, a body weight loss, hypertrophy of the adrenals,26 hypersecretion of corticosterone,38 and sleep abnormalities.24 However, this stress regimen did not. induce particular anxiety symptoms in two animal models of anxiety, the elevated plus-maze and the social interaction tests.37 Therefore, this simulation Inhibitors,research,lifescience,medical elicits behavioral and physiological abnormalities found in depression, and these effects seem to have some specificity for depressive-like behaviors. Predictive validity Trie different types of antidepressant drugs did not. modify reinforced behaviors in control nonstressed

animals. Medications Inhibitors,research,lifescience,medical effective in antagonizing stress-induced anhedonia include representatives of the tricyclics11,19 monoamine reuptake inhibitors such as fluoxetine and maprotiline,27 Anacetrapib inhibitors of monoamine oxidase such as moclobemide and brofaromine,20,28 and atypical antidepressants such as mianserin.21,39 Electroconvulsive shocks24 and lithium40 are also active in this model. The antagonism of stress-induced anhedonia requires 2 to 4 weeks of treatment, similar to the time course of antidepressant drugs in humans. Inefficacious substances include representatives of tranquilizers such as chlordiazepoxide27; antipsychotics such as risperidone (see above), haloperidol, and chlorprothixene; psychostimulants such as amphetamine; and analgesics such as morphine.28 Therefore, this simulation appears as specific and selective in its response to all categories of clinically used antidepressant treatments, and in its lack of response to other nonantidepressant psychotropics.