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. 2022 Dec;59(12):7170-7181.
doi: 10.1007/s12035-022-03022-y. Epub 2022 Sep 19.

Imipramine Can Be Effective on Depressive-Like Behaviors, but Not on Neurotrophic Factor Levels in an Animal Model for Bipolar Disorder Induced by Ouabain

Taise Possamai-Della  1 , Gustavo C Dal-Pont  2 , Wilson R Resende  1 , Jorge M Aguiar-Geraldo  1 , Jefté Peper-Nascimento  1 , João Quevedo  1   3   4   5 , Samira S Valvassori  6
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Imipramine Can Be Effective on Depressive-Like Behaviors, but Not on Neurotrophic Factor Levels in an Animal Model for Bipolar Disorder Induced by Ouabain

Taise Possamai-Della et al. Mol Neurobiol. 2022 Dec.

Abstract

Introduction: Despite possible risks of mania switching with the long-term use of antidepressants in patients with bipolar disorder (BD), these drugs may help in depressive episodes. Alterations in neurotrophic factor levels seem to be involved in the pathophysiology of BD. The present study aimed to evaluate the effect of acute treatment of imipramine on behavior and neurotrophic levels in rats submitted to the animal model for BD induced by ouabain.

Methods: Wistar rats received a single intracerebroventricular (ICV) injection of artificial cerebrospinal fluid or ouabain (10-3 M). Following the ICV administration, the rats were treated for 14 days with saline (NaCl 0.9%, i.p.), lithium (47.5 mg/kg, i.p.), or valproate (200 mg/kg, i.p.). On the 13th and 14th days of treatment, the animals received an additional injection of saline or imipramine (10 mg/kg, i.p.). Behavior tests were evaluated 7 and 14 days after ICV injection. Adrenal gland weight and concentrations of ACTH were evaluated. Levels of neurotrophins BDNF, NGF, NT-3, and GDNF were measured in the frontal cortex and hippocampus by ELISA test.

Results: The administration of ouabain induced mania- and depressive-like behavior in the animals 7 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 imipramine alone can be effective on depressive-like symptoms but not on neurotrophic factor alterations present in BD.

Keywords: Antidepressant; Bipolar disorder; Imipramine; Neurotrophins.

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References

    1. Smith DJ, Whitham EA, Ghaemi SN (2012) Bipolar disorder. Handb Clin Neurol 106:251–263. https://doi.org/10.1016/B978-0-444-52002-9.00015-2 - DOI - PubMed
    1. Miller JN, Black DW (2020) Bipolar disorder and suicide: a review. Curr Psychiatry Rep 22(2):6. https://doi.org/10.1007/s11920-020-1130-0 - DOI - PubMed
    1. American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders (DSM-5®), 5th edn. American Psychiatric Publishing, Washinton (DC) - DOI
    1. Wu R, Fan J, Zhao J, Calabrese JR, Gao K (2014) The relationship between neurotrophins and bipolar disorder. Expert Rev Neurother 14(1):51–65. https://doi.org/10.1586/14737175.2014.863709 - DOI - PubMed
    1. Gibon J, Barker PA (2017) Neurotrophins and proneurotrophins: focus on synaptic activity and plasticityin the brain. Neuroscientist 23(6):587–604. https://doi.org/10.1177/1073858417697037 - DOI - PubMed