Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
Biol Psychiatry. 2011 Aug 1;70(3):298-304. doi: 10.1016/j.biopsych.2011.01.026. Epub 2011 Apr 8.
There are no drugs that specifically target the social deficits of autism spectrum disorders (ASD). This may be due to a lack of behavioral paradigms in animal models relevant to ASD. Partner preference formation in the prairie vole represents a social cognitive process involving socially reinforced learning. D-cycloserine (DCS) is a cognitive enhancer that acts at the N-methyl-D-aspartate receptor to promote learning. If DCS enhances socially reinforced learning in the partner preference paradigm, it may be useful in combination with behavioral therapies for enhancing social functioning in ASD.
Female prairie and meadow voles were given DCS either peripherally or directly into one of three brain regions: nucleus accumbens, amygdala, or caudate putamen. Subjects were then cohabited with a male vole under conditions that do not typically yield a partner preference. The development of a preference for that stimulus male vole over a novel male vole was assessed using a partner preference test.
A low dose of DCS administered peripherally enhanced preference formation in prairie voles but not meadow voles under conditions in which it would not otherwise occur. These effects were replicated in prairie voles by microinfusions of DCS into the nucleus accumbens, which is involved in reinforcement learning, and the amygdala, which is involved in social information processing.
Partner preference in the prairie vole may provide a behavioral paradigm with face, construct, and predictive validity for identifying prosocial pharmacotherapeutics. D-cycloserine may be a viable treatment strategy for social deficits of ASD when paired with social behavioral therapy.
目前尚无专门针对自闭症谱系障碍（ASD）社交缺陷的药物。这可能是由于缺乏与 ASD 相关的动物模型中的行为范式。草原田鼠的伴侣偏好形成代表了一种涉及社交强化学习的社会认知过程。D-环丝氨酸（DCS）是一种作用于 N-甲基-D-天冬氨酸受体以促进学习的认知增强剂。如果 DCS 增强伴侣偏好范式中的社交强化学习，它可能与行为疗法结合使用，增强 ASD 的社交功能。
雌性草原田鼠和草地田鼠给予 DCS 外周或直接注入三个脑区之一：伏隔核、杏仁核或尾壳核。然后，将这些动物与一只雄性田鼠同居，这些条件通常不会产生伴侣偏好。使用伴侣偏好测试评估对该刺激雄性田鼠的偏好相对于新雄性田鼠的发展。
外周给予低剂量的 DCS 增强了草原田鼠的偏好形成，但不会增强草地田鼠的偏好形成，即使在不会发生偏好的情况下也是如此。通过将 DCS 微注入参与强化学习的伏隔核和参与社会信息处理的杏仁核，在草原田鼠中复制了这些效应。
草原田鼠的伴侣偏好可能为识别亲社会药物治疗提供具有面部、结构和预测有效性的行为范式。当与社交行为疗法结合使用时，D-环丝氨酸可能是 ASD 社交缺陷的可行治疗策略。
