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

丙咪嗪在用乌巴因预先处理的大鼠中诱发多动症:对抗抑郁药诱发的躁狂症转换的影响

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作者:Samira S Valvassori, José H Cararo, Carlos Augusto P Marino, Taise Possamai-Della, Camila L Ferreira, Jorge M Aguiar-Geraldo, Gustavo C Dal-Pont, João Quevedo

Background

Bipolar disorder (BD) is a psychiatric disorder with complex therapy, besides the treatment with antidepressants induce a mania switch.

Conclusion

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.

Methods

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.

Objective

Investigate the effect of the administration of imipramine (IMI) in rats submitted to intracerebroventricular (ICV) administrations of ouabain (OUA).

Results

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.

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