Effects of chronic social defeat on behavioral and neural correlates of sociality: Vasopressin, oxytocin and the vasopressinergic V1b receptor
Effects of chronic social defeat on behavioral and neural correlates of sociality: Vasopressin, oxytocin and the vasopressinergic V1b receptor
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DOI：
10.1016/j.physbeh.2011.03.007
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发表时间：
2011-06
影响因子：
2.9
通讯作者：
Y. Litvin;G. Murakami;D. Pfaff
中科院分区：
文献类型：
--
作者：
Y. Litvin;G. Murakami;D. Pfaff
啮齿类动物的慢性社会压力产生的行为和神经内分泌模式类似于人类精神病理学相关的症状。小鼠的慢性社交失败已被用于研究与压力相关的社交障碍的遗传和表观遗传前体。神经肽精氨酸加压素（AVP）和催产素（OT）在中枢靶点释放，分别调节反社会和亲社会行为。AVP结合到与焦虑、抑郁和亲和行为相关的离散大脑区域中的V1 a和V1 b受体（V1 bRs）。最近的证据表明，V1 bR与压力和焦虑有关，可能是治疗相关疾病的一个有吸引力的靶点。在本系列实验中，我们旨在评估慢性社会失败压力对以下方面的影响：1）社会调查范式中的焦虑相关行为及其通过急性剂量的V1 bR拮抗剂SSR 149415的潜在调节; 2）下丘脑室旁核（PVN）中AVP和Fos蛋白水平; 3）与社交性相关的脑区域中AVP和OT受体（OTR）mRNA水平。当与不败动物相比时，社交失败的小鼠对一种新的雄性同种动物表现出致焦虑行为特征，SSR 149415部分减弱了这些作用。免疫荧光组织化学显示，失败产生的Fos和AVP和Fos蛋白在下丘脑室旁核（PVN）的双标记显着升高。SSR 149415减弱了失败对Fos和AVP/Fos双标记的影响，与抗焦虑作用一致。失败的小鼠表现出水平升高的OTR mRNA水平在外侧隔（LS），除了增加V1 bR和OTR mRNA在内侧杏仁核（MeA）。我们建议参与的V1 bRs和OTRs的电路涉及PVN，MeA和LS的失败对社会性的影响。SSR 149415减弱了社会调查模型中的焦虑发生以及Fos和AVP/Fos标记，表明V1 bRs是治疗焦虑的有吸引力的靶标，特别是社交障碍。
Chronic social stress in rodents produces behavioral and neuroendocrine patterns analogous to symptoms associated with psychopathologies in humans. Chronic social defeat in mice has been used to study the genetic and epigenetic precursors of stress-related social disorders. The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) are released in central targets to modulate anti- and pro-social behaviors, respectively. AVP binds to V1a and V1b receptors (V1bRs) in discrete brain regions related to anxiety, depression and affiliative behaviors. Recent evidence suggests that V1bRs are involved in stress and anxiety and may be an attractive target for the treatment of associated disorders.In the present series of experiments, we aimed to evaluate the effects of chronic social defeat stress on: 1) anxiety-related behaviors in a social investigation paradigm and their potential modulation by an acute dose of SSR149415, a V1bR antagonist; 2) AVP and Fos protein levels in the paraventricular nucleus of the hypothalamus (PVN) and; 3) AVP- and OT-receptor (OTR) mRNA levels in brain regions associated with sociality. When compared to undefeated animals, socially defeated mice exhibited an anxiogenic behavioral profile towards a novel male conspecific, with SSR149415 partly attenuating these effects. Histochemistry using immunofluorescence showed defeat produced significant elevations of Fos and double labeling of AVP and Fos proteins in the paraventricular nucleus of the hypothalamus (PVN). SSR149415 attenuated the effects of defeat on Fos and AVP/Fos double labeling, consistent with an anxiolytic effect. Defeated mice showed elevated levels of OTR mRNA levels in the lateral septum (LS) in addition to increased V1bR and OTR mRNA in the medial amygdala (MeA). We suggest the involvement of V1bRs and OTRs in a circuit involving the PVN, MeA and LS in the effects of defeat on sociality. SSR149415 attenuated anxiogenesis in the social investigation model and both Fos and AVP/Fos labeling, suggesting V1bRs are an attractive target for the treatment of anxiety in general and disorders of sociality in particular.