Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, 400715, China; Faculty of Psychology, Southwest University, Chongqing, 400715, China; Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA.
College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, Jiangsu 225009, China; Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA.
Neuropharmacology. 2018 Jan;128:96-105. doi: 10.1016/j.neuropharm.2017.09.037. Epub 2017 Sep 28.
Serotonin 5-HT 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-HT receptor is involved in. We first showed that activation of 5-HT receptor by TCB-2 (a highly selective 5-HT agonist, 1, 2.5 or 5.0 mg/kg) disrupted maternal behavior dose-dependently, and this effect was reduced by pretreatment with a 5-HT receptor antagonist MDL 100907, but exacerbated by pretreatment with a 5-HT receptor antagonist SB242084 and a 5-HT receptor agonist MK212, indicating that the maternal disruptive effect of 5-HT activation is receptor-specific and can be modulated by 5-HT 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-HT 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-HT). Functional disruption of this neuroreceptor system might contribute to postpartum mental disorders (e.g. depression and psychosis) that impair the quality of maternal care.
5-羟色胺 5-HT 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、学习和记忆中发挥重要作用。我们研究了其在大鼠母性行为中的作用，母性行为是一种自然行为，包含许多涉及 5-HT 受体的心理功能。我们首先表明，5-HT 受体激动剂 TCB-2（一种高度选择性的 5-HT 激动剂，1、2.5 或 5.0mg/kg）激活可剂量依赖性地破坏母性行为，这种作用可被 5-HT 受体拮抗剂 MDL 100907 预处理减弱，但可被 5-HT 受体拮抗剂 SB242084 和 5-HT 受体激动剂 MK212 预处理增强，表明 5-HT 激活的母性行为破坏作用是受体特异性的，可被 5-HT 受体双向调节。然后，我们将 TCB-2 微注射到两个对正常表达母性行为很重要的脑区：内侧前额叶皮层（mPFC）和内侧视前区（mPOA），发现只有急性 mPFC 内注射 TCB-2 会抑制幼仔的寻回，而 mPOA 内注射则没有影响。最后，使用 c-Fos 免疫组化，我们发现腹侧终纹床核（vBNST）、中央杏仁核（CeA）和背侧中缝核（DR）也参与了 TCB-2 的母性行为破坏作用。这些发现表明，mPFC 中的 5-HT 受体和其他与母性行为相关的区域中的 5-HT 受体通过其内在作用或与其他受体（如 5-HT）的相互作用，对于正常表达母性行为是必需的。该神经受体系统的功能障碍可能导致产后精神障碍（如抑郁和精神病），从而损害母婴护理的质量。
