Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy
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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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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 / OxytocinSource:
Psychoneuroendocrinology, 2021, 129Publisher:
- 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
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PharmacyTY - 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 . .