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It is known that cognitive processes, such as learning and memory, are affected in depression. Several authors have described histone deacetylase (HDAC) inhibitors as a class of drugs that improves long-term memory formation. The current study examined the effects of maternal deprivation (MD) and chronic mild stress (CMS), which have been shown as animal models of depression, and the effects of sodium butyrate (SB), a HDAC inhibitor, on recognition memory. Considering that neurotrophic factors has been pointed as a key event involved with cognition and depressive disorder, levels of neurotrophic factors (BDNF, NGF and GDNF) were also investigated. MD and CMS induced depressive-like behavior in the forced swimming test (FST) and memory impairment in the object recognition (OR) test, without altering locomotor activity of rats. In addition, SB was able to reverse the stress-induced neurotrophic factors decrease and reversed memory impairment. The results indicate that the stress both at early and later stage of life may induce cognitive impairment in animals and neurotrofic factors (BDNF, NGF and GDNF) levels decrease. SB treatment improved the recognition memory and reversed the neurotrophins levels decreased in the hippocampus of rats submitted to the MD and CMS models. Together, our results reinforce the notion that SB displays a specific antidepressant profile and improve cognition in MD and CMS rats that may be, at least in part, due to its upregulation of neurotrophic factors.

Improving our understanding of oxidative damage in biomolecules, antioxidant mechanisms and the inflammatory system - alterations presented in the animal models of mania - is important in helping us to improve our knowledge concerning the pathophysiology of BD, and the mechanisms of action employed by mood stabilizers.

The aim of the present study was to evaluate the effects of sodium butyrate on depressive-like behavior and mitochondrial alteration parameters in animal models of depression induced by maternal deprivation or chronic mild stress in Wistar rats. maternal deprivation was established by separating pups from their mothers for 3 h daily from postnatal day 1 to day 10. Chronic mild stress was established by water deprivation, food deprivation, restraint stress, isolation and flashing lights. Sodium butyrate or saline was administered twice a day for 7 days before the behavioral tests. Depressive behavior was evaluated using the forced swim test. The activity of tricarboxylic acid cycle enzymes (succinate dehydrogenase and malate dehydrogenase) and of mitochondrial chain complexes (I, II, II-III and IV) was measured in the striatum of rats. From these analyses it can be observed that sodium butyrate reversed the depressive-like behavior observed in both animal models of depression. Additionally, maternal deprivation and chronic mild stress inhibited mitochondrial respiratory chain complexes and increased the activity of tricarboxylic acid cycle enzymes. Sodium butyrate treatment reversed -maternal deprivation and chronic mild stress- induced dysfunction in the striatum of rats. In conclusion, sodium butyrate showed antidepressant effects in maternal deprivation and chronic mild stress-treated rats, and this effect can be attributed to its action on the neurochemical pathways related to depression.

A particular challenge in the development of a bipolar disorder (BD) model in animals is the complicated clinical course of the condition, characterized by manic, depressive and mixed mood episodes. Ouabain (OUA) is an inhibitor of Na + /K + -ATPase enzyme. Intracerebroventricular (ICV) injection of this drug in rats has been regarded a proper model to study BD by mimic specific manic symptoms, which are reversed by lithium (Li), an important mood stabilizer drug. However, further validation of this experimental approach is required to characterize it as an animal model of BD, including depressive-like behaviors. The present study aimed to assess manic- and depressive-like behaviors, potential alteration in the hypothalamic-pituitary-adrenal (HPA) system and oxidative stress parameters after a single OUA ICV administration in adult male Wistar rats. Moreover, we evaluated Li effects in this experimental setting. Data show that OUA ICV administration could constitute a suitable model for BD since the injection of the drug triggered manic- and depressive-like behaviors in the same animal. Additionally, the OUA model mimics significant physiological and neurochemical alterations detected in BD patients, including an increase in oxidative stress and change in HPA axis. Our findings suggest that decreased Na + /K + -ATPase activity detected in bipolar patients may be linked to increased secretion of glucocorticoid hormones and oxidative damage, leading to the marked behavioral swings. The Li administration mitigated these pathological changes in the rats. The proposed OUA model is regarded as suitable to simulate BD by complying with all validities required to a proper animal model of the psychiatric disorder.

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