您的位置:首页 > 学术动态

高军副教授和李鸣教授团队在母性行为调控机制研究上取得重要进展

发布时间:2017-11-01 来源:本站原创 作者:本站编辑   浏览次数:

近日,高军副教授和李鸣教授团队在著名的神经药理学专业杂志《Neuropharmacology》(SCI收录Q1)上发表题为“Activation of 5-HT2A receptor disrupts rat maternal behavior”(激活五羟色胺2A受体破坏大鼠母性行为)文章,文章的通讯作者是高军副教授和李鸣教授,同时高军副教授和武瑞勇为文章的共同第一作者。

母性行为是一种复杂的本能社会行为,对母亲的健康以及子代的生存和发展都具有重要意义。中枢五羟色胺系统调控多种心理功能,包括感觉运动门控、情绪、动机、学习记忆、执行控制等。母性行为的启动和维持需要五羟色胺系统调控的这些心理功能的密切参与。但对母性行为的五羟色胺调控机制目前研究较少,特别是对相关的神经受体和中枢调控机制缺乏足够了解。

心理学部动物实验中心高军副教授和李鸣教授团队以啮齿类动物大鼠的母性行为为模型,采用行为药理学、中枢微量给药、免疫组织化学等技术来系统考察了这一问题。近期,在相关的神经受体和中枢调控机制方面取得重要进展。该研究通过五个实验系统考察了大鼠母性行为调控的五羟色胺 2A 受体及其中枢机制。该研究首次在大鼠上直接证实了五羟色胺2A受体是调控母性行为的关键受体机制。五羟色胺 2A可以特异性的破坏母性行为的表达,并且发现五羟色胺的另外一种受体2C亚型的激活或抑制都会加强该破坏作用。通过对中枢的免疫组织化学及中枢给药的直接干预研究发现了内侧前额叶(mPFC)、腹侧终纹床核(vBNST)、杏仁核及背侧中缝核是可能的关键调节脑区。研究者通过本研究及团队其他研究认为五羟色胺2A受体是通过影响母性动机和情绪加工过程来调控母性行为的,这些神经受体的功能异常可能是导致产后精神疾病患者母性行为下降的重要机制之一。

高军副教授和李鸣教授研究团队的研究重点就是关注调控母性行为的心理学及神经生物学机制,团队同时也关注精神类药物对心理功能的长期影响的神经及心理机制。母性行为的研究对于认识良好的母性行为表达的神经心理基础、揭示产后抑郁等产后精神疾病方面都具有重要意义。

该研究得到国家自然科学基金和中央高校基本科研业务费及 NIH基金的资助。

 

Gao, J., Wu, R., Davis, C., Li, M., Activation of 5-HT2A receptor disrupts rat maternal behavior, Neuropharmacology (2017), doi: 10.1016/j.neuropharm.2017.09.037.

原文摘要:

Serotonin 5-HT2A receptor is widely distributed in the central nervous system and plays an important role in sensorimotor function, emotion regulation, motivation, executive control, learning and memory. We investigated its role in rat maternal behavior, a naturalistic behavior encompassing many psychological functions that the 5-HT2A receptor is involved in. We first showed that activation of 5-HT2A receptor by TCB-2 (a highly selective 5-HT2A agonist, 1, 2.5 or 5.0 mg/kg) disrupted maternal behavior dose-dependently, and this effect was reduced by pretreatment with a 5-HT2A receptor antagonist MDL 100907, but exacerbated by pretreatment with a 5-HT2C receptor antagonist SB242084 and a 5-HT2C receptor agonist MK212, indicating that the maternal disruptive effect of 5-HT2A activation is receptor-specific and can be modulated by 5-HT2C receptor bidirectionally. We then microinjected TCB-2 into two brain regions important for the normal expression of maternal behavior: the medial prefrontal cortex (mPFC) and the medial preoptic area (mPOA) and found that only acute intra-mPFC infusion of TCB-2 suppressed pup retrieval, whereas intra-mPOA had no effect. Finally, using c-Fos immunohistochemistry, we identified that the ventral bed nucleus of stria terminalis (vBNST), the central amygdala (CeA), and the dorsal raphe (DR) were additionally involved in the maternal-disruptive effect of TCB-2. These findings suggest that the 5-HT2A receptor in the mPFC and other maternally related regions is required for the normal expression of maternal behavior through its intrinsic action or interactions with other receptors (e.g. 5-HT2C). Functional disruption of this neuroreceptor system might contribute to postpartum mental disorders (e.g. depression and psychosis) that impair the quality of maternal care.