Targeting the Oxytocin System to Ameliorate Early Life Depressive-Like Behaviors in Maternally-Separated Rats
Targeting the Oxytocin System to Ameliorate Early Life Depressive-Like Behaviors in Maternally-Separated Rats
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DOI：
10.1248/bpb.b21-00247
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发表时间：
2021-10-01
影响因子：
2
通讯作者：
El-Khatib, Aiman S.
中科院分区：
文献类型：
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作者：
Abdelwahab, Lobna A.;Galal, Omneya O.;El-Khatib, Aiman S.
催产素（OXT）——“爱的荷尔蒙”——参与了一些选择性血清素再摄取抑制剂（SSRIs）的抗抑郁活性。抑郁症中OXT通路的确切机制尚不完全清楚。本研究旨在探讨OXT类似物卡贝菌素（CBT）和SSRI艾司西酞普兰（ESCIT）对产妇分离（MS）后抑郁样行为的影响。值得一提的是，鼻内CBT已被美国食品和药物管理局（FDA）批准用于治疗Prader-Willi综合征。分别给母分离成年Wistar白化大鼠单独或联合给予CBT （100 μ g/只/d，通过吸入方式）和ESCIT (20 mg kg（-1)，每只（p.o）），疗程为7d。重复3小时MS显示强迫游泳测试（FST）中静止时间增加，开阔场地测试中运动活动减少。MS升高血浆促肾上腺皮质激素（ACTH）水平，但显著降低血浆OXT，对海马OXT- r表达无影响。MS后海马5-羟色胺受体（5HT1A-R）、血清素转运体（SERT）含量升高。CBT和ESCIT可纠正FST的行为障碍，抑制高水平ACTH。此外，两种治疗都提高了OXT水平，降低了5HT1A-R和正常化SERT含量，这反映了血清素的可用性增加。CBT能显著改善MS引起的组织病理损伤，抑制胶质原纤维酸性蛋白的升高。CBT和ESCIT通过积极影响血清素和催产素系统来控制抑郁样行为。利用cbt靶向OXT系统改善母亲分离诱导的抑郁样行为，可能是通过提高OXT血浆水平、降低激素ACTH、恢复海马催产素表达和血清素机制。
Oxytocin (OXT) -"the love hormone"- has been involved in the anti-depressant activity of some selective serotonin reuptake inhibitors (SSRIs). The exact mechanism underlying the OXT pathway in depression is not fully clear. This study aimed to investigate the effect of OXT analogue, carbetocin (CBT) and the SSRI, escitalopram (ESCIT) on depressive-like behaviors following maternal separation (MS). It is worthy to mention that intranasal CBT has been approved by U.S. Food and Drug Administration (FDA) for Prader-Willi syndrome. Adolescent Wistar albino maternally-separated rats were given CBT, (100 mu g/animal/d via inhalation route), and, ESCIT, (20 mg kg(-1), per os (p.o.)) either alone or in combination for 7d. Repeated 3-h MS demonstrated increased immobility time in forced swim test (FST) and decreased locomotor activity in open field test. MS elevated plasma level of adrenocortico-trophic hormone (ACTH) but notably reduced plasma OXT, with no effect on hippocampal OXT-R expression. Following MS, hippocampal contents of 5-hydroxytryptamine receptors (5HT1A-R), serotonin transporter (SERT) were increased. CBT and ESCIT corrected the behavioral dysfunction in FST and suppressed the high levels of ACTH. Additionally, both treatments boosted OXT level, reduced 5HT1A-R and normalized SERT contents, which reflects increased availability of serotonin. Finally, CBT markedly ameliorated the histopathological damage induced by MS and suppressed the increased glial fibrillary acidic protein. CBT and ESCIT manage depressive-like behavior by positively affecting serotonergic and oxytocinergic systems. Targeting OXT system -using CBT-ameliorated depressive like behaviors induced by maternal separation most probably via enhancing OXT plasma levels, attenuating hormonal ACTH and restoring the expression of hippocampal oxytocin and serotonin mechanisms.