Esketamine and Rapastinel, but not Imipramine, have antidepressant-like effect in a treatment-resistant animal model of depression

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Esketamine and Rapastinel, but not Imipramine, have antidepressant-like effect in a treatment-resistant animal model of depression. / Pereira, Vitor Silva; Joca, Sâmia R L; Harvey, Brian H et al.

In: Acta Neuropsychiatrica, Vol. 31, No. 5, 10.2019, p. 258-265.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Pereira, Vitor Silva ; Joca, Sâmia R L ; Harvey, Brian H et al. / Esketamine and Rapastinel, but not Imipramine, have antidepressant-like effect in a treatment-resistant animal model of depression. In: Acta Neuropsychiatrica. 2019 ; Vol. 31, No. 5. pp. 258-265.

Bibtex

@article{e459755713d64733a6bd7b7bf7171d3b,
title = "Esketamine and Rapastinel, but not Imipramine, have antidepressant-like effect in a treatment-resistant animal model of depression",
abstract = "OBJECTIVE: 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 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 (NMDA) receptor in ACTH-treated animals.METHODS: Na{\"i}ve male Sprague Dawley rats were subjected to repeated subcutaneous injections with ACTH (100 µg/0.1mL/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 confirms 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 antidepressants.",
keywords = "Adrenocorticotropic Hormone, Depression, GLYX-13 peptide, esketamine, rat",
author = "Pereira, {Vitor Silva} and Joca, {S{\^a}mia R L} and Harvey, {Brian H} and Betina Elfving and Gregers Wegener",
year = "2019",
month = oct,
doi = "10.1017/neu.2019.25",
language = "English",
volume = "31",
pages = "258--265",
journal = "Acta Neuropsychiatrica",
issn = "0924-2708",
publisher = "Cambridge University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Esketamine and Rapastinel, but not Imipramine, have antidepressant-like effect in a treatment-resistant animal model of depression

AU - Pereira, Vitor Silva

AU - Joca, Sâmia R L

AU - Harvey, Brian H

AU - Elfving, Betina

AU - Wegener, Gregers

PY - 2019/10

Y1 - 2019/10

N2 - OBJECTIVE: 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 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 (NMDA) receptor in ACTH-treated animals.METHODS: Naïve male Sprague Dawley rats were subjected to repeated subcutaneous injections with ACTH (100 µg/0.1mL/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 confirms 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 antidepressants.

AB - OBJECTIVE: 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 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 (NMDA) receptor in ACTH-treated animals.METHODS: Naïve male Sprague Dawley rats were subjected to repeated subcutaneous injections with ACTH (100 µg/0.1mL/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 confirms 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 antidepressants.

KW - Adrenocorticotropic Hormone

KW - Depression

KW - GLYX-13 peptide

KW - esketamine

KW - rat

U2 - 10.1017/neu.2019.25

DO - 10.1017/neu.2019.25

M3 - Journal article

C2 - 31230597

VL - 31

SP - 258

EP - 265

JO - Acta Neuropsychiatrica

JF - Acta Neuropsychiatrica

SN - 0924-2708

IS - 5

ER -