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Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy

Authorized Users Only
2021
Authors
Stanić, Dušanka
Oved, Keren
Israel-Elgali, Ifat
Jukić, Marin
Batinić, Bojan
Puškaš, Nela
Shomron, Noam
Gurwitz, David
Pešić, Vesna
Article (Published version)
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Abstract
Intranasal treatment with oxytocin showed beneficial effects in post-traumatic stress disorder and autism spectrum disorders; however, it was not investigated as much in depression. Keeping in mind the favorable effects of oxytocin on animal models of anxiety and depression, we postulated that synergy between prescribed first choice drugs, selective serotonin reuptake inhibitors (SSRIs) and oxytocin could improve the treatment outcome compared with SSRI monotherapy. Our previous in vitro genome-wide transcriptomic study on human lymphoblastoid cell lines exposed to paroxetine resulted in increase of integrin β3 (ITGB3) gene expression, and further, ITGB3/CHL1 expression ratio was hypothesized to influence the sensitivity to SSRIs. The aim of this report was to explore molecular mechanisms behind the antidepressant-like oxytocin effect, alone and in synergy with citalopram, on behavioral and molecular level in corticosterone treated rats, a paradigm used to model anxiety and depression ...in animals. Oxytocin treatment (1) ameliorated corticosterone-induced reduction of neurogenesis and number of parvalbumin-positive interneurons in the hippocampal CA1 region, (2) enhanced anxiolytic- and antidepressant-like effects of citalopram in the open field test, and (3) the SSRI/oxytocin synergy persisted in reversing the reduction of the Itgb3 gene expression and increased Itgb3/Chl1 ratio in the prefrontal cortices. These results support the existence of synergy between citalopram and oxytocin in reversing the molecular and behavioral changes induced by corticosterone treatment and point to possible molecular mechanisms behind antidepressant-like effect of oxytocin.

Keywords:
Citalopram / Depression / Itgb3/Chl1 / Oxytocin
Source:
Psychoneuroendocrinology, 2021, 129
Publisher:
  • Elsevier Ltd
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200161 (University of Belgrade, Faculty of Pharmacy) (RS-200161)
  • Biomarkers of organ damage and dysfunction (RS-175036)

DOI: 10.1016/j.psyneuen.2021.105234

ISSN: 0306-4530

WoS: 000661462300004

Scopus: 2-s2.0-85105831227
[ Google Scholar ]
2
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/3883
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Stanić, Dušanka
AU  - Oved, Keren
AU  - Israel-Elgali, Ifat
AU  - Jukić, Marin
AU  - Batinić, Bojan
AU  - Puškaš, Nela
AU  - Shomron, Noam
AU  - Gurwitz, David
AU  - Pešić, Vesna
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3883
AB  - Intranasal treatment with oxytocin showed beneficial effects in post-traumatic stress disorder and autism spectrum disorders; however, it was not investigated as much in depression. Keeping in mind the favorable effects of oxytocin on animal models of anxiety and depression, we postulated that synergy between prescribed first choice drugs, selective serotonin reuptake inhibitors (SSRIs) and oxytocin could improve the treatment outcome compared with SSRI monotherapy. Our previous in vitro genome-wide transcriptomic study on human lymphoblastoid cell lines exposed to paroxetine resulted in increase of integrin β3 (ITGB3) gene expression, and further, ITGB3/CHL1 expression ratio was hypothesized to influence the sensitivity to SSRIs. The aim of this report was to explore molecular mechanisms behind the antidepressant-like oxytocin effect, alone and in synergy with citalopram, on behavioral and molecular level in corticosterone treated rats, a paradigm used to model anxiety and depression in animals. Oxytocin treatment (1) ameliorated corticosterone-induced reduction of neurogenesis and number of parvalbumin-positive interneurons in the hippocampal CA1 region, (2) enhanced anxiolytic- and antidepressant-like effects of citalopram in the open field test, and (3) the SSRI/oxytocin synergy persisted in reversing the reduction of the Itgb3 gene expression and increased Itgb3/Chl1 ratio in the prefrontal cortices. These results support the existence of synergy between citalopram and oxytocin in reversing the molecular and behavioral changes induced by corticosterone treatment and point to possible molecular mechanisms behind antidepressant-like effect of oxytocin.
PB  - Elsevier Ltd
T2  - Psychoneuroendocrinology
T1  - Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy
VL  - 129
DO  - 10.1016/j.psyneuen.2021.105234
ER  - 
@article{
author = "Stanić, Dušanka and Oved, Keren and Israel-Elgali, Ifat and Jukić, Marin and Batinić, Bojan and Puškaš, Nela and Shomron, Noam and Gurwitz, David and Pešić, Vesna",
year = "2021",
abstract = "Intranasal treatment with oxytocin showed beneficial effects in post-traumatic stress disorder and autism spectrum disorders; however, it was not investigated as much in depression. Keeping in mind the favorable effects of oxytocin on animal models of anxiety and depression, we postulated that synergy between prescribed first choice drugs, selective serotonin reuptake inhibitors (SSRIs) and oxytocin could improve the treatment outcome compared with SSRI monotherapy. Our previous in vitro genome-wide transcriptomic study on human lymphoblastoid cell lines exposed to paroxetine resulted in increase of integrin β3 (ITGB3) gene expression, and further, ITGB3/CHL1 expression ratio was hypothesized to influence the sensitivity to SSRIs. The aim of this report was to explore molecular mechanisms behind the antidepressant-like oxytocin effect, alone and in synergy with citalopram, on behavioral and molecular level in corticosterone treated rats, a paradigm used to model anxiety and depression in animals. Oxytocin treatment (1) ameliorated corticosterone-induced reduction of neurogenesis and number of parvalbumin-positive interneurons in the hippocampal CA1 region, (2) enhanced anxiolytic- and antidepressant-like effects of citalopram in the open field test, and (3) the SSRI/oxytocin synergy persisted in reversing the reduction of the Itgb3 gene expression and increased Itgb3/Chl1 ratio in the prefrontal cortices. These results support the existence of synergy between citalopram and oxytocin in reversing the molecular and behavioral changes induced by corticosterone treatment and point to possible molecular mechanisms behind antidepressant-like effect of oxytocin.",
publisher = "Elsevier Ltd",
journal = "Psychoneuroendocrinology",
title = "Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy",
volume = "129",
doi = "10.1016/j.psyneuen.2021.105234"
}
Stanić, D., Oved, K., Israel-Elgali, I., Jukić, M., Batinić, B., Puškaš, N., Shomron, N., Gurwitz, D.,& Pešić, V.. (2021). Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy. in Psychoneuroendocrinology
Elsevier Ltd., 129.
https://doi.org/10.1016/j.psyneuen.2021.105234
Stanić D, Oved K, Israel-Elgali I, Jukić M, Batinić B, Puškaš N, Shomron N, Gurwitz D, Pešić V. Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy. in Psychoneuroendocrinology. 2021;129.
doi:10.1016/j.psyneuen.2021.105234 .
Stanić, Dušanka, Oved, Keren, Israel-Elgali, Ifat, Jukić, Marin, Batinić, Bojan, Puškaš, Nela, Shomron, Noam, Gurwitz, David, Pešić, Vesna, "Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy" in Psychoneuroendocrinology, 129 (2021),
https://doi.org/10.1016/j.psyneuen.2021.105234 . .

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