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Objective: The present study aims to investigate the effects of Lithium (Li) on manic- and depressive-like behaviors and inflammatory parameters in rats submitted to the bipolar disorder (BD) model induced by ouabain (OUA). Material and methods: Adult male rats received a single intracerebroventricular (ICV) injection of OUA or artificial cerebrospinal fluid (aCSF). On the fourth day after the ICV injection, the rats received intraperitoneal injections of saline (NaCl 0.9%) or Li (47.5 mg/kg), two times a day, for 14 days. On the seventh day after OUA injection, the locomotor activity was assessed (open field test), and on the fourteenth day, locomotion was evaluated again, which was followed by the forced swimming test to evaluate depressive-like behavior. After euthanasia, inflammatory parameters were evaluated in the frontal cortex and hippocampus. Results: After seven days of OUA administration, the animals showed a hyperactive behavior that was reversed by treatment with Li. After 14 days of ICV injections, rats exhibited a depressive behavior. Regarding the inflammatory parameters, measured after 14 days of the ICV infusions, OAU induced an increase in the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α, and cytokine-induced neutrophil chemoattractant-1. In contrast, Li treatment decreased these parameters. Conclusion: The animal model of BD induced by an OUA is able to induce neuroinflammation, which supports its construct validity for the BD research.

Introduction: Despite the risk of mania switch to long-term administration of antidepressants in bipolar disorder (BD) patients, an acute administration of these drugs can help in depressive episodes. Furthermore, alterations in neurotrophic factor levels seem to be part of the BD’s physiopathology. Therefore, the aim of the present study is to evaluate the effect of acute treatment of imipramine on behavior and neurotrophins levels in rats submitted to the animal model of BD induced by ouabain. Methods: Wistar rats received a single intracerebroventricular (ICV) injection of artificial cerebrospinal fluid or ouabain. The rats were treated for 14 days with saline, lithium, or valproate. On the 13th and 14th days of treatment, the animals received an additional injection of saline or imipramine. Behavior tests were evaluated seven and 14 days after ICV injection. Adrenal gland weight and levels of ACTH were evaluated. Levels of BDNF, NGF, NT-3, and GDNF were measured in the frontal cortex and hippocampus. Results: The administration of ouabain induced mania- and depressive-like behavior in the animals seven and 14 days after ICV, respectively. The treatment with lithium and valproate reversed the mania-like behavior. All treatments were able to reverse most of the depressive-like behaviors induced by ouabain. Moreover, ouabain increased HPA-axis parameters in serum and decreased the neurotrophin levels in the frontal cortex and hippocampus. All treatments, except imipramine, reversed these alterations. Conclusion: It can be suggested that acute administration of IMI alone can be effective on depressive-like symptoms but not on neurotrophic factors alterations present in BD.