Long-term exposure to intranasal oxytocin in a mouse autism model.
Long-term exposure to intranasal oxytocin in a mouse autism model.
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DOI：
10.1038/tp.2014.117
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发表时间：
2014-11-11
影响因子：
6.8
通讯作者：
Mendoza SP
中科院分区：
文献类型：
--
作者：
Bales KL;Solomon M;Jacob S;Crawley JN;Silverman JL;Larke RH;Sahagun E;Puhger KR;Pride MC;Mendoza SP
催产素(OT)是一种参与哺乳动物社会行为的神经肽。它目前正处于治疗自闭症谱系障碍(ASD)的临床试验中。之前对健康啮齿动物(草原田鼠和C57BL/6J小鼠)的研究表明，长期鼻腔给药可能会产生有害影响，这引发了关于安全性和有效性的问题。为了研究OT对ASD表型的影响，我们首次在BTBR T+Itpr3tf/J近交系(BTBR)的自闭症小鼠模型上进行了慢性鼻腔OT的研究，该模型表现出低社交能力和高重复行为。BTBR和C57BL/6J(B6)小鼠(N=94)从第21天开始滴鼻注射催产素0.8 IU/kg，每日1次，连续30天。我们运行了一套与自闭症诊断和相关症状相关的行为任务，包括青少年互惠社交活动、三室社交方法、开放领域探索活动、重复的自我修饰和恐惧条件下的学习和记忆，其中一些是在治疗期间和之后进行的。鼻腔催产素没有改善BTBR中与自闭症相关的行为，除了在三室社会互动测试中女性嗅探。生理盐水处理的雄性BTBR小鼠在室内时间和嗅觉时间上都表现出对新小鼠的兴趣增加，而OT处理的雄性BTBR小鼠仅在嗅觉时间上表现出对新小鼠的偏好。在B6或BTBR小鼠中都没有检测到OT的有害影响，除了可能在OT处理的雄性BTBR小鼠中缺乏对新鼠室的偏好。这些结果突显了理解OT对行为的影响所固有的复杂性。未来鼻腔慢性催产素的研究应该包括更广泛的剂量范围和在健康啮齿动物和ASD模型中的早期发育时间点，以确认催产素的有效性和安全性。
Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8 IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT.
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影响因子：
3.9
作者：
Dadds, Mark R.;MacDonald, Elayne;Brennan, John
通讯作者：
Brennan, John
影响因子：
3
作者：
Curley, James P.;Davidson, Stephanie;Champagne, Frances A.
通讯作者：
Champagne, Frances A.
DOI：
10.1111/gbb.12115
发表时间：
2014-03
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Brielmaier J;Senerth JM;Silverman JL;Matteson PG;Millonig JH;DiCicco-Bloom E;Crawley JN
通讯作者：
Crawley JN
影响因子：
4.7
作者：
Chadman, Kathryn K.;Gong, Shiaoching;Crawley, Jacqueline N.
通讯作者：
Crawley, Jacqueline N.
DOI：
10.1073/pnas.1015316108
发表时间：
2011-01-25
影响因子：
11.1
作者：
De Dreu, Carsten K. W.;Greer, Lindred L.;Handgraaf, Michel J. J.
通讯作者：
Handgraaf, Michel J. J.