Imipramine induces hyperactivity in rats pretreated with ouabain: Implications to the mania switch induced by antidepressants

• Published in: Journal of affective disorders 2022-02, Vol.299, p.425-434
• Main Authors: Valvassori, Samira S., Cararo, José H., Marino, Carlos Augusto P., Possamai-Della, Taise, Ferreira, Camila L., Aguiar-Geraldo, Jorge M., Dal-Pont, Gustavo C., Quevedo, João
• Format: Article
• Language: English
• Subjects: Animals; Antidepressant; Antidepressive Agents; Depressive episodes; Disease Models, Animal; Humans; Imipramine - pharmacology; Mania; Mania switch; Ouabain; Ouabain - toxicity; Oxidative stress; Rats; Rats, Wistar
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2021.12.021

•Imipramine induces hyperactivity in rats.•The OUA model of BD could be used as a tool to study bipolar disorder in the context of mania switch.•Alterations in the Na+K+atpase could be involved in the manic-switch.•A drug as IMI can to trigger molecular alterations leading to mania switch. Bipolar disorder (BD) is a psychiatric disorder with complex therapy, besides the treatment with antidepressants induce a mania switch. Investigate the effect of the administration of imipramine (IMI) in rats submitted to intracerebroventricular (ICV) administrations of ouabain (OUA). Adult Wistar rats (n = 28) were submitted to only one ICV administration of OUA or artificial cerebrospinal fluid. On the 7th and 9th days following the ICV administration, animals were submitted to a behavioral analysis comprising open field task and forced swimming test. Between the 9th and 14th days, the rats received one daily intraperitoneal administration of IMI or saline (Sal). On the 15th day rats were submitted to the last session of behavioral analysis, followed by euthanasia. The frontal cortex and hippocampus were dissected for the subsequent biochemical assessments: oxidative parameters, and Na+/K+-ATPase activity. OUA administration induced a manic-like effect on the 7th day and a depressive-like behavior on the 14th day. In contrast, IMI administration elicited significant mania switch-like effect on this same stage in animals who received OUA. OUA increased oxidative damage and activity of antioxidant enzymes in the brain of rats. IMI potentialized the oxidative damage of OUA. No significant differences between groups were observed in the Na+/K+-ATPase activity. The present study suggests that residual effects from inhibition of the Na+K+ATPase could be involved in the manic-switch observed in bipolar patients. Besides, the OUA model of bipolar disorder could be used to study bipolar disorder in the context of mania switch.