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dc.contributor.authorPereira, Vitor Silva
dc.contributor.authorHarvey, Brian H.
dc.contributor.authorJoca, Sâmia R.L.
dc.contributor.authorElfving, Betina
dc.contributor.authorWegener, Gregers
dc.date.accessioned2019-07-11T11:07:16Z
dc.date.available2019-07-11T11:07:16Z
dc.date.issued2019
dc.identifier.citationPereira, V.S. et al. 2019. Esketamine and rapastinel, but not imipramine, have antidepressant-like effect in a treatment-resistant animal model of depression. Acta neuropsychiatrica, 31(5):258-265. [https://doi.org/10.1017/neu.2019.25]en_US
dc.identifier.issn0924-2708
dc.identifier.issn1601-5215 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/32853
dc.identifier.urihttps://doi.org/10.1017/neu.2019.25
dc.description.abstractObjectives: Treatment-resistance to antidepressants is a major problem in the pharmacotherapy of major depressive disorder (MDD). Unfortunately, only a few animal models are suitable for studying treatment-resistant depression, among them repeated treatment with Adrenocorticotropic hormone (ACTH) appears to be useful to mimic treatment-resistance to monoaminergic antidepressants. Therefore, the present work aimed to investigate the effectiveness of s-ketamine and rapastinel (formerly GLYX13), modulators of the glutamatergic N-methyl-D-aspartate receptor in ACTH-treated animals. Methods: Naïve male Sprague Dawley rats were subjected to repeated subcutaneous injections with ACTH (100 µg/0.1 ml/rat/day) for 14 days and drug treatment on the test day (open field and forced swim test) with imipramine, s-ketamine or rapastinel. In addition, assessment of plasma levels of corticosterone and ACTH was carried out. Results: We found that rats repeatedly treated with ACTH for 14 days responded to single injections with s-ketamine (15 mg/kg) and rapastinel (10 mg/kg), but failed to respond to imipramine (15 mg/kg). In the plasma, the levels of corticosterone and ACTH were increased after 14 days of daily treatment with ACTH, independently of the treatment. Conclusion: The present data confirm development of a resistance to treatment following chronic ACTH administration. In addition, the study confirms the possible effectiveness of s-ketamine and rapastinel as treatment options in treatment-resistant depression. Moreover, it highlights the importance of the glutamatergic system in the neurobiology of depression. Further studies are necessary to evaluate how repeated treatment with ACTH leads to a depressed condition resistant to monoaminergic antidepressantsen_US
dc.language.isoenen_US
dc.publisherCambridge Univ Pressen_US
dc.subjectAdrenocorticotropic hormoneen_US
dc.subjectDepressionen_US
dc.subjectEsketamineen_US
dc.subjectGLYX-13 peptideen_US
dc.subjectRaten_US
dc.titleEsketamine and rapastinel, but not imipramine, have antidepressant-like effect in a treatment-resistant animal model of depressionen_US
dc.typeArticleen_US
dc.contributor.researchID11083417 - Harvey, Brian Herbert


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