Parker Karen J, Buckmaster Christine L, Schatzberg Alan F, Lyons David M
Department of Psychiatry and Behavioral Sciences, Stanford University Medical School, CA 94305-5485, USA.
Psychoneuroendocrinology. 2005 Oct;30(9):924-9. doi: 10.1016/j.psyneuen.2005.04.002.
Social relationships protect against the development of stress-related psychiatric disorders, yet little is known about the neurobiology that regulates this phenomenon. Recent evidence suggests that oxytocin (OT), a neuropeptide involved in social bond formation, may play a role. This experiment investigated the effects of chronic intranasal OT administration on acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation in adult female squirrel monkeys. Subjects were randomized to one of two experimental conditions. Monkeys were intranasally administered either 50 microg oxytocin (N = 6 monkeys) or 0 microg oxytocin (N = 6 monkeys)/300 microl saline once a day for eight consecutive days. Immediately after drug administration on the eighth day, all monkeys were exposed to acute social isolation. Blood samples for determinations of adrenocorticotropic hormone (ACTH) and cortisol concentrations were collected after 30 and 90 min of stress exposure. Consistent with an anti-stress effect, OT-treated monkeys exhibited lower ACTH concentrations compared to saline-treated monkeys after 90 min of social isolation (F(1,7) = 6.891; P = 0.034). No drug-related differences in cortisol levels were observed, indicating that OT does not directly attenuate the adrenal stress response. Intranasal peptide administration has been shown to penetrate the central nervous system, and research must determine whether intranasally delivered OT exerts its effect(s) at a pituitary and/or brain level. This primate model offers critical opportunities to improve our understanding of the anti-stress effects of OT and may lead to novel pharmacological treatments for stress-related psychiatric disorders.
社会关系能够预防与压力相关的精神疾病的发生，然而，对于调节这一现象的神经生物学机制我们却知之甚少。最近的证据表明，催产素（OT），一种参与社会联系形成的神经肽，可能发挥了作用。本实验研究了成年雌性松鼠猴长期经鼻给予OT对急性应激诱导的下丘脑-垂体-肾上腺（HPA）轴激活的影响。将实验对象随机分为两种实验条件之一。猴子连续八天每天经鼻给予50微克催产素（N = 6只猴子）或0微克催产素（N = 6只猴子）/300微升生理盐水。在第八天给药后立即将所有猴子暴露于急性社会隔离环境中。在应激暴露30分钟和90分钟后采集血样以测定促肾上腺皮质激素（ACTH）和皮质醇浓度。与抗应激作用一致，在社会隔离90分钟后，经OT处理的猴子与经生理盐水处理的猴子相比，ACTH浓度较低（F(1,7) = 6.891；P = 0.034）。未观察到皮质醇水平存在与药物相关的差异，这表明OT不会直接减弱肾上腺应激反应。经鼻给予肽已被证明可穿透中枢神经系统，并且研究必须确定经鼻给予的OT是否在垂体和/或大脑水平发挥其作用。这个灵长类动物模型为增进我们对OT抗应激作用的理解提供了关键机会，并且可能会带来针对与压力相关的精神疾病的新型药物治疗方法。
