Nitric oxide (NO) have been recently related to depression. The administration of NO synthase (NOS) inhibitors induce antidepressant-like effects in animal models and there is an increase in the NOS expression in limbic structures of depressive humans and stressed animals. There is also known that stressful events increase the activation of limbic structures neurons and that antidepressants and the NOS inhibitor 7-NI, decrease this activation. However, how these limbic structures nitrergic system is related to the behavioral consequences of stress and depression, is still unknown. Our objective is to test the hypothesis that the development of helpless behavior (a behavior related to depression) in rats would be due to an increase in NO-containing neurons activation in some structures related to behavioral and emotional consequences of stress. The different treatments would induce an antidepressant-like effect in this model, sharing a final commom effect of decrease this activation and consequently decrease de NO levels. We will use rats, submitted to the learned helplessness model of depression treated with antidepressants or 7-NI. After the test, the brain slices will be submitted to a histochemical process to double-labeling neurons for fos (neuronal activation marker) and NADPH-diaphorase (NOS-containing neurons) and to nitrotirosine (indirect measurement of local NO augmentation). Nitrite quantification (by Griess - an indirect measurement of NO levels) and western blotting for phosphorylated-nNOS and iNOS will also be made, to determine if the NO produced is provenient from which NOS isoform.
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