D-cycloserine improves sociability and spontaneous stereotypic behaviors in 4-week old mice
D-cycloserine improves sociability and spontaneous stereotypic behaviors in 4-week old mice
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DOI：
10.1016/j.brainres.2011.12.040
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发表时间：
2012-02-23
期刊：
影响因子：
2.9
通讯作者：
Benson, Andrew D.
中科院分区：
文献类型：
--
作者：
Deutsch, Stephen I.;Pepe, Gerald J.;Benson, Andrew D.
BALB/c小鼠是与自闭症谱系障碍(ASD)相关的社交能力和社会动机受损的模型。8周龄Balb/c小鼠的社交能力受损可被NMDA受体上甘氨酸(B)位置的激动剂(如D-环丝氨酸)减弱。尽管自闭症通常在蹒跚学步的时候被发现，但人们对更早地发现(例如，在6个月前)和疾病修改干预以改善功能结果感兴趣。因此，我们想知道D-环丝氨酸是否能改善4周龄Balb/c小鼠的社交能力，与其对8周龄小鼠的效果相似。D-环丝氨酸改善了4周龄(即断奶后一周)Balb/c小鼠社交能力受损的程度。此外，由于刻板印象可以与社会刺激的显着性竞争，我们比较了Balb/c和瑞士韦伯斯特老鼠在与社会刺激老鼠进行社交互动时出现的几种自发刻板印象行为。有趣的是，与8周大的小鼠类似，4周大的瑞士韦伯斯特小鼠在社交互动中的自发刻板印象行为更加强烈；此外，D-环丝氨酸降低了它们的强度。因此，D-环丝氨酸改善了社交能力和刻板行为，但这些作用可能缺乏品系选择性。低剂量D-环丝氨酸对Balb/c小鼠有亲社会作用。D-环丝氨酸具有治疗自闭症所需药物的治疗特性；具体地说，药物不应以恶化社交能力为代价来改善刻板印象行为，反之亦然。这些数据表明，靶向NMDA受体可以在自闭症精神病理学的两个突出领域产生良好的治疗效果：社交能力受损和自发的刻板行为。(C)2012爱思唯尔B.V.保留所有权利。
Balb/c mice are a model of impaired sociability and social motivation relevant to autism spectrum disorders (ASDs). Impaired sociability of 8-week old Balb/c mice is attenuated by agonists of the glycine(B) site on the NMDA receptor, such as D-cycloserine. Although ASDs are often recognized in toddlerhood, there is interest in earlier identification (e.g., before 6 months) and disease-modifying interventions to improve functional outcomes. Thus, we wondered if D-cycloserine could improve sociability in 4-week old Balb/c mice, similar to its effects in 8-week old mice. D-Cycloserine improved measures of impaired sociability in 4-week old (i.e., one-week post-weanling) Balb/c mice. Moreover, because stereotypies can compete with the salience of social stimuli, we compared Balb/c and Swiss Webster mice on several spontaneous stereotypic behaviors emerging during social interaction with a social stimulus mouse. Interestingly, similar to 8-week old mice, spontaneous stereotypic behaviors during social interaction were more intense in the 4-week old Swiss Webster mice; furthermore, D-cycloserine reduced their intensity. Thus, D-cycloserine improves both sociability and stereotypic behaviors, but these effects may lack strain-selectivity. A prosocial effect of D-cycloserine was observed at a dose as low as 32.0 mg/kg in Balb/c mice. D-cycloserine has the therapeutic properties of a desired medication for ASDs; specifically, a medication should not improve stereotypic behaviors at the expense of worsening sociability and vice versa. The data suggest that targeting the NMDA receptor can have promising therapeutic effects on two prominent domains of psychopathology in ASDs: impaired sociability and spontaneous stereotypic behaviors. (C) 2012 Elsevier B.V. All rights reserved.