Lawson Sarah K, Gray Andrew C, Woehrle Nancy S
Department of Psychology, Wittenberg University, Springfield, OH 45501 United States.
Department of Psychology, Wittenberg University, Springfield, OH 45501 United States; Neuroscience Program, Wittenberg University, Springfield, OH 45501, United States.
Behav Brain Res. 2016 Nov 1;314:52-64. doi: 10.1016/j.bbr.2016.07.027. Epub 2016 Jul 18.
Social impairments in autism remain poorly understood and without approved pharmacotherapies. Novel animals models are needed to elucidate mechanisms and evaluate novel treatments for the social deficits in autism. Recently, serotonin 1B receptor (5-HT1B) agonist challenge in mice was shown to induce autism-like behaviors including perseveration, reduced prepulse inhibition, and delayed alternation deficits. However, the effects of 5-HT1B agonists on autism-related social behaviors in mice remain unknown. Here, we examine the effects of 5-HT1B agonist challenge on sociability and preference for social novelty in mice. We also examine the effects of 5-HT1B agonist treatment on average rearing duration, a putative rodent measure of non-selective attention. Non-selective attention is an associated feature of autism that is also not well understood. We show that 5-HT1B receptor activation reduces sociability, preference for social novelty, and rearing in mice. In addition, we examine the ability of oxytocin, an off-label treatment for the social impairments in autism, to reverse 5-HT1B agonist-induced social and attention deficits in mice. We show that oxytocin restores social novelty preference in mice treated with a 5-HT1B agonist. We also show that oxytocin attenuates 5-HT1B agonist-induced sociability and rearing deficits in mice. Our results suggest that 5-HT1B agonist challenge provides a useful pharmacological mouse model for aspects of autism, and implicate 5-HT1B in autism social and attention deficits. Moreover, our findings suggest that oxytocin may treat the social deficits in autism through a mechanism involving 5-HT1B.
自闭症中的社交障碍仍未得到充分理解，且尚无获批的药物疗法。需要新的动物模型来阐明其机制并评估针对自闭症社交缺陷的新疗法。最近，研究表明给小鼠注射血清素1B受体（5-HT1B）激动剂会诱发类似自闭症的行为，包括持续性动作、前脉冲抑制降低和延迟交替缺陷。然而，5-HT1B激动剂对小鼠自闭症相关社交行为的影响仍不清楚。在此，我们研究了5-HT1B激动剂激发对小鼠社交能力和对社交新奇性偏好的影响。我们还研究了5-HT1B激动剂治疗对平均竖毛持续时间的影响，这是一种推测的啮齿动物非选择性注意力指标。非选择性注意力是自闭症的一个相关特征，目前也尚未完全理解。我们发现5-HT1B受体激活会降低小鼠的社交能力、对社交新奇性的偏好以及竖毛行为。此外，我们研究了催产素（一种未被批准用于治疗自闭症社交障碍的药物）逆转5-HT1B激动剂诱导的小鼠社交和注意力缺陷的能力。我们发现催产素可恢复用5-HT1B激动剂处理的小鼠对社交新奇性的偏好。我们还发现催产素可减轻5-HT1B激动剂诱导的小鼠社交能力和竖毛行为缺陷。我们的结果表明，5-HT1B激动剂激发为自闭症的某些方面提供了一种有用的药理学小鼠模型，并表明5-HT1B与自闭症社交和注意力缺陷有关。此外，我们的研究结果表明，催产素可能通过涉及5-HT1B的机制来治疗自闭症的社交缺陷。
