Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy. (July 2021)

• Record Type: Journal Article
• Authors: Stanić, Dušanka; Oved, Keren; Israel-Elgali, Ifat; Jukić, Marin; Batinić, Bojan; Puškaš, Nela; Shomron, Noam; Gurwitz, David; Pešić, Vesna
• Is Part Of: Psychoneuroendocrinology. Volume 129(2021)
• Publication Date: 2021-07
• Subjects: Oxytocin -- Citalopram -- Depression -- Itgb3/Chl1; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2021.105234
• Languages: English
• ISSNs: 0306-4530

Abstract

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. Highlights: Oxytocin combined with citalopram attenuates increased despair and anxiety-like behavior. Oxytocin improves differentiation and survival of hippocampal neuronal progenitors. Reduced BDNF expression in hippocampus was ameliorated by oxytocin. Loss of PV+ GABA signaling was restored in CA1 but not in CA2/3 by oxytocin. Itgb3/Chl1 ratio, potential marker of SSRI response, was reduced in our depression model. Reduction of Itgb3/Chl1 was fully recovered by combined oxytocin/citalopram treatment.