Hippocampal Microinfusion of Oxytocin Attenuates the Behavioural Response to Stress by Means of Dynamic Interplay with the Glucocorticoid-Catecholamine Responses
Hippocampal Microinfusion of Oxytocin Attenuates the Behavioural Response to Stress by Means of Dynamic Interplay with the Glucocorticoid-Catecholamine Responses
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DOI：
10.1111/j.1365-2826.2010.02003.x
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发表时间：
2010-08-01
影响因子：
3.2
通讯作者：
Zohar, J.
中科院分区：
文献类型：
--
作者：
Cohen, H.;Kaplan, Z.;Zohar, J.
神经垂体激素催产素充当中枢神经系统神经递质/神经调质。我们评估了催产素对压力行为反应的影响，以及相关的生物生理反应，在一个受控的，前瞻性的动物模型。对雄性大鼠海马微量注射外源性催产素的长期效应进行了评估。将动物暴露于捕食者气味应激，并在1小时或7天后用催产素或载体处理。行为进行了评估与高架十字迷宫和声惊吓反应测试，7天后显微注射和冷冻行为暴露于创伤相关的线索在第8天。这些数据用于分类为行为反应组。评估创伤提示反应、循环皮质酮和催产素、糖皮质激素和盐皮质激素受体的海马表达以及催产素受体mRNA水平。催产素，皮质酮和去甲肾上腺素之间的相互作用进行了评估。在捕食者气味应激暴露后立即或7天后，暴露于创伤线索后微量输注催产素显著降低了极端反应者的患病率，并降低了创伤线索冻结反应。暴露后处理与催产素显着纠正皮质酮应激反应，减少糖皮质激素受体的表达和增加盐皮质激素受体表达的海马体相比，车辆处理。大剂量皮质酮与去甲肾上腺素联合给药引起血浆催产素和海马催产素受体的释放。催产素积极参与捕食者气味应激过程的神经生物学反应，因此值得进一步研究，作为治疗焦虑相关疾病的潜在治疗途径。
The neurohypophysial hormone oxytocin acts as a central nervous system neurotransmitter/neuromodulator. We evaluated the effects of oxytocin on behavioural responses to stress, as well as associated biophysiological responses, in a controlled, prospective animal model. The long-term effects of exogenous oxytocin microinjected to the hippocampus of male rats were assessed. Animals were exposed to predator scent stress and treated 1 h or 7 days later with oxytocin or vehicle. Behaviours were assessed with the elevated plus-maze and acoustic startle response tests, 7 days after microinjection and freezing behaviour upon exposure to a trauma-related cue on day 8. These data served for classification into behavioural response groups. Trauma cue response, circulating corticosterone and oxytocin, hippocampal expression of glucocorticoid and mineralocorticoid receptors, and oxytocin receptor mRNA levels were assessed. The interplay between oxytocin, corticosterone and norepinephrine was assessed. Microinfusion of oxytocin both immediately after predator scent stress exposure or 7 days later, after exposure to trauma cue significantly reduced the prevalence rates of extreme responders and reduced trauma cue freezing responses. Post-exposure treatment with oxytocin significantly corrected the corticosterone stress response, decreased glucocorticoid receptor expression and increased mineralocorticoid receptor expression in the hippocampus compared to vehicle treatment. High-dose corticosterone administration together with norepinephrine caused release of plasma oxytocin and hippocampal oxytocin receptor. Oxytocin is actively involved in the neurobiological response to predator scent stress processes and thus warrants further study as a potential therapeutic avenue for the treatment of anxiety-related disorders.