Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute of Mental Health, NIH, Bethesda, Maryland 20892-3730, USA.
Autism Res. 2011 Feb;4(1):17-27. doi: 10.1002/aur.163. Epub 2010 Oct 6.
Behavioral therapies are currently the most effective interventions for treating the diagnostic symptoms of autism. We employed a mouse model of autism to evaluate components of behavioral interventions that improve sociability in mice. BTBR T+tf/J (BTBR) is an inbred mouse strain that exhibits prominent behavioral phenotypes with face validity to all three diagnostic symptom categories of autism, including robust and well-replicated deficits in social approach and reciprocal social interactions. To investigate the role of peer interactions in the development of sociability, BTBR juvenile mice were reared in the same home cage with juvenile mice of a highly social inbred strain, C57BL/6J (B6). Subject mice were tested as young adults for sociability and repetitive behaviors. B6 controls reared with B6 showed their strain-typical high sociability. BTBR controls reared with BTBR showed their strain-typical lack of sociability. In contrast, BTBR reared with B6 as juveniles showed significant sociability as young adults. A 20-day intervention was as effective as a 40-day intervention for improving social approach behavior. High levels of repetitive self-grooming in BTBR were not rescued by peer-rearing with B6, indicating specificity of the intervention to the social domain. These results from a robust mouse model of autism support the interpretation that social enrichment with juvenile peers is a beneficial intervention for improving adult outcome in the social domain. This novel paradigm may prove useful for discovering factors that are essential for effective behavioral treatments, and biological mechanisms underlying effective behavioral interventions.
行为疗法目前是治疗自闭症诊断症状最有效的干预措施。我们使用自闭症小鼠模型来评估改善小鼠社交能力的行为干预措施的组成部分。BTBR T+tf/J(BTBR)是一种近交系小鼠,具有自闭症所有三个诊断症状类别的明显行为表型,包括社交接近和互惠社交互动方面的强大且经过充分复制的缺陷。为了研究同伴互动在社交能力发展中的作用,BTBR 幼年小鼠与高度社交的近交系 C57BL/6J(B6)幼年小鼠在同一个笼中饲养。作为年轻成年人,对受试小鼠进行社交能力和重复行为测试。与 B6 一起饲养的 B6 对照品系表现出其典型的高社交性。与 BTBR 一起饲养的 BTBR 对照品系表现出其典型的缺乏社交性。相比之下,作为幼鼠与 B6 一起饲养的 BTBR 在成年时表现出显著的社交能力。20 天的干预与 40 天的干预一样有效,可以改善社交接近行为。与 B6 同伴饲养并不能挽救 BTBR 中高水平的重复自我梳理行为,表明干预措施对社交领域具有特异性。这种来自自闭症强大小鼠模型的结果支持了这样的解释,即与幼年同伴进行社交丰富是改善社交领域成年结果的有益干预措施。这种新的范式可能有助于发现对有效行为治疗至关重要的因素,以及有效行为干预的生物学机制。