Yee Jason R, Kenkel William M, Frijling Jessie L, Dodhia Sonam, Onishi Kenneth G, Tovar Santiago, Saber Maha J, Lewis Gregory F, Liu Wensheng, Porges Stephen W, Carter C Sue
Northeastern University, United States; The Kinsey Institute at Indiana University, United States.
Northeastern University, United States; The Kinsey Institute at Indiana University, United States.
Horm Behav. 2016 Apr;80:82-91. doi: 10.1016/j.yhbeh.2016.01.010. Epub 2016 Feb 4.
The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic-pituitary-adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behavioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25mg/kg) or OXT antagonist (OXT-A, 20mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pretreatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore, OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors.
神经肽催产素（OXT）促进亲社会行为和选择性社交。在应激情况下，OXT还可下调下丘脑-垂体-肾上腺（HPA）轴的活性，这使得人们考虑将OXT作为治疗多种社会情感障碍的潜在药物。然而，外源性OXT在应激环境中调节社会行为的机制尚未完全明确。在此，我们研究了以下假设：自主神经通路是OXT在可能引发动员行为反应的应激环境中协助募集社会资源的机制组成部分。雌性草原田鼠（Microtus ochrogaster）在腹腔注射OXT（0.25mg/kg）或OXT拮抗剂（OXT-A，20mg/kg）预处理后经历应激源（在浅水中行走），并在有或没有同笼伙伴的情况下恢复。注射OXT导致血浆中OXT浓度升高，但并未减弱HPA轴对应激源的反应。然而，OXT预处理（而非OXT-A预处理）可防止通常在无OXT时出现的室旁核（PVN）活性（通过c-Fos免疫反应性测量）与HPA输出（即皮质酮释放）之间的功能偶联。此外，OXT预处理导致PVN活性与调节自主神经系统交感神经（即延髓头端腹外侧）和副交感神经（即迷走背核复合体和疑核）分支的脑区之间产生功能偶联。这些发现表明，OXT增强了对自主神经活动的中枢神经控制，而非严格减弱HPA轴的活性，并提供了一种潜在机制，通过该机制OXT可能促进对应激源的适应性和情境依赖性行为及生理反应。
