Activation of 5-HT(2A) receptor disrupts rat maternal behavior.
Activation of 5-HT(2A) receptor disrupts rat maternal behavior.
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5-HT2A 受体的激活扰乱了大鼠的母性行为
DOI：
10.1016/j.neuropharm.2017.09.037
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发表时间：
2018-01
影响因子：
4.7
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Gao J;Wu R;Davis C;Li M
5-HT 2A受体广泛分布于中枢神经系统，在感觉运动功能、情绪调节、动机、执行控制、学习记忆等方面发挥重要作用。我们研究了它在大鼠母性行为中的作用，这是一种自然主义行为，包括5-HT 2A受体参与的许多心理功能。我们首先发现TCB-2对5-HT 2A受体的激活作用，（高选择性5-HT 2A激动剂，1、2.5或5.0 mg/kg）剂量依赖性地破坏母体行为，并且这种作用通过用5-HT 2A受体拮抗剂MDL 100907预处理而降低，但通过用5-HT 2C受体拮抗剂SB 242084和5-HT 2C受体激动剂MK 212预处理而加重，表明5-HT 2A激活的母体破坏作用是受体特异性的，并且可以由5-HT 2C受体双向调节。然后，我们将TCB-2显微注射到两个对母体行为的正常表达很重要的大脑区域：内侧前额叶皮层（mPFC）和内侧视前区（mPOA），发现只有急性mPFC内TCB-2输注抑制了幼崽的检索，而mPOA内没有影响。最后，使用c-Fos免疫组织化学，我们确定终纹腹侧床核（vBNST）、中央杏仁核（CeA）和中缝背核（DR）还参与了TCB-2的母体破坏作用。这些发现表明，mPFC和其他母性相关区域中的5-HT 2A受体通过其内在作用或与其他受体（例如5-HT 2C）的相互作用，是母性行为正常表达所必需的。这种神经感受器系统的功能中断可能会导致产后精神障碍（如抑郁症和精神病），从而影响产妇护理的质量。
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.
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影响因子：
3.7
作者：
Bubar MJ;Stutz SJ;Cunningham KA
通讯作者：
Cunningham KA
5-羟色胺2C受体激动剂MK212和2A受体拮抗剂MDL100907对产后雌性大鼠母性行为的影响。
影响因子：
3.6
作者：
Chen, Weihai;Zhang, Qi;Su, Wenxin;Zhang, Haorong;Yang, Yu;Qiao, Jing;Sui, Nan;Li, Ming
通讯作者：
Li, Ming
影响因子：
3.6
作者：
Di Matteo, V;Cacchio, M;Esposito, E
通讯作者：
Esposito, E
影响因子：
17.7
作者：
Bhagwagar, Zubin;Hinz, Rainer;Grasby, Paul
通讯作者：
Grasby, Paul
影响因子：
3.2
作者：
Bosch, O. J.;Pfoertsch, J.;Neumann, I. D.
通讯作者：
Neumann, I. D.