Thèse observations point, to the similarity with the clinical situation where (i) in depressed patients, at. least.

2 to 3 weeks of treatment are necessary before observing a significant mood improvement; and (ii) antidepressant drugs do not, PLX-4720 modify mood in nondepressed individuals. These pharmacological data allow chronic mild stressinduced Inhibitors,research,lifescience,medical anhedonia in rats to be considered as a simulation of human depression exhibiting a fair predictive validity for drug therapy of affective disorders. In order to further substantiate this validity, we tested the effects of a nonpharmacological treatment, of depression, namely electroshock therapy. This treatment is used in severe cases of depression not responding to classic antidepressant, medication. Electroshock therapy is recognized as being more efficacious and more rapidly acting than chemotherapy.22,23 Thus, we tested the effects of electroshock treatment in Inhibitors,research,lifescience,medical anhedonic rats.24 Results are presented in Figure 4. Figure 4. Curative effects of electroshock treatment on stress-induced anhedonia .Variations of self-stimulation threshold in stressed (from day 1 to day 33) rats treated (from day 21 to day 33) with 6 electroshocks (open circles) or sham shocks (blue squares) … In both groups of animals, the stress regimen

induced an anhedonic Inhibitors,research,lifescience,medical state that, gradually developed over a 2-week period. When “depressed” animals were submitted to an electroshock on dav 21, their anhedonic state was completely and very rapidly reversed. Inhibitors,research,lifescience,medical In contrast, anhedonia of stressed animals submitted to sham shocks was not significantly diminished. Electroshock treatment was found to be much more rapid than antidepressant medications. These results provide an interesting parallel with the clinical situation where, in certain

cases, nonresponder depressed patients exhibited a rapid Inhibitors,research,lifescience,medical and profound mood elevation following electroconvulsive therapy Indeed, it. has long been known that patients responding to electroshocks often exhibit, a rapid loss of their depressive symptomatology.25 A final step in evaluating the predictive validity of this simulation consisted in verifying its specificity for antidepressant treatments. To this purpose, the effects of the antipsychotic drug PDK4 risperidone were evaluated in stressed animals. As shown in Figure 5, 26 all stressed rats developed an anhedonic state, whether they were treated with placebo or with risperidone. Preventative treatment with this antipsychotic drug remained inefficient, in suppressing stress-induced anhedonia. Risperidone by itself increased self-stimulation threshold in nonstressed animals. This could explain the loss of an antianhedonic effect in stressed animals. Risperidone blocks both dopaminergic D2 and serotonergic 5-HT2 receptors.