Postpartum Lactation-Mediated Behavioral Outcomes and Drug Responses in a Spontaneous Mouse Model of Obsessive-Compulsive Disorder.
Postpartum Lactation-Mediated Behavioral Outcomes and Drug Responses in a Spontaneous Mouse Model of Obsessive-Compulsive Disorder.
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强迫症自发小鼠模型中产后哺乳介导的行为结果和药物反应。
DOI：
10.1021/acschemneuro.7b00231
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发表时间：
2017
影响因子：
5
通讯作者：
Bult-Ito,Abel
中科院分区：
文献类型：
--
作者：
Mitra,Swarup;Mucha,McKenzie;Owen,Savanah;Bult-Ito,Abel
使用自发的强迫症(OCD)小鼠模型，本研究评估了产后哺乳对强迫样行为表达的影响、SSRI有效性，以及催产素和多巴胺在调节这些哺乳期特异性行为结果中的假定作用。强迫型哺乳期小鼠在筑巢和大理石埋葬方面不那么强迫型，与强迫型非哺乳期和未分娩的雌性相比，对氟西汀(50 mg/kg)的反应增强。与未分娩的雌性相比，哺乳期小鼠在旷场测试中表现出更多的焦虑样行为，而慢性氟西汀减少了焦虑样行为。用L368-899(5 mg/kg)阻断哺乳期小鼠的催产素受体，可加重强迫行为和抑郁行为。多巴胺D2受体(D2R)激动剂溴隐亭(10 mg/kg)抑制了大理石埋藏、筑巢和在开阔场地的中央进入，但由于它也抑制了在开阔场地的整体活动，D2R受体的激活可能非特异性地抑制了整体活动。因此，哺乳期和氟西汀介导的强迫症样小鼠的行为结果似乎部分受到催产素能机制的调节。与非哺乳期和未分娩的强迫症小鼠相比，哺乳期强迫症小鼠的5-羟色胺免疫反应性和血清水平更高。综上所述，这些结果表明，在类强迫症小鼠的哺乳期，行为调节、5-羟色胺能变化以及SSRI有效性的变化。这需要对强迫症患者的产后事件进行进一步的调查。
Using a spontaneous mouse model of obsessive–compulsive disorder (OCD), the current study evaluated the influence of postpartum lactation on the expression of compulsive-like behaviors, SSRI effectiveness, and the putative role of oxytocin and dopamine in mediating these lactation specific behavioral outcomes. Compulsive-like lactating mice were less compulsive-like in nest building and marble burying and showed enhanced responsiveness to fluoxetine (50 mg/kg) in comparison to compulsive-like nonlactating and nulliparous females. Lactating mice exhibited more anxiety-like behavior in the open field test compared to the nulliparous females, while chronic fluoxetine reduced anxiety-like behaviors. Blocking the oxytocin receptor with L368-899 (5 mg/kg) in the lactating mice exacerbated the compulsive-like and depression-like behaviors. The dopamine D2 receptor (D2R) agonist bromocriptine (10 mg/kg) suppressed marble burying, nest building, and central entries in the open field, but because it also suppressed overall locomotion in the open field, activation of the D2R receptor may have inhibited overall activity nonspecifically. Lactation- and fluoxetine-mediated behavioral outcomes in compulsive-like mice, therefore, appear to be partly regulated by oxytocinergic mechanisms. Serotonin immunoreactivity and serum levels were higher in lactating compulsive-like mice compared to nonlactating and nulliparous compulsive-like females. Together, these results suggest behavioral modulation, serotonergic alterations, and changes in SSRI effectiveness during lactation in compulsive-like mice. This warrants further investigation of postpartum events in OCD patients.