Chronic icv oxytocin attenuates the pathological high anxiety state of selectively bred Wistar rats
Chronic icv oxytocin attenuates the pathological high anxiety state of selectively bred Wistar rats
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DOI：
10.1016/j.neuropharm.2009.06.038
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发表时间：
2010-01
影响因子：
4.7
通讯作者：
David A. Slattery;I. D. Neumann
中科院分区：
文献类型：
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作者：
David A. Slattery;I. D. Neumann
中枢催产素 (OXT) 已被证明可以促进多种社会行为、减弱 HPA 轴的激素应激反应并减少焦虑。分别针对高 (HAB) 和低 (LAB) 焦虑相关行为选择性培育的 Wistar 大鼠已被证明是一种合适的动物模型，可用于研究焦虑和抑郁相关疾病等精神病理学的潜在病因学。本研究的目的是评估中枢 OXT 对雄性和雌性 HAB 和 LAB 大鼠焦虑和抑郁相关行为的影响。根据明暗箱评估，急性 icv OXT（1 μg）或 OXT 受体拮抗剂（OXT-A；0.75 μg）给药不会影响雄性或雌性 HAB 和 LAB 大鼠的焦虑相关行为。相比之下，长期icv OXT输注（10ng/h；6d）减弱了雌性HAB大鼠而非雄性HAB大鼠的高水平焦虑相关行为，而慢性OXT-A输注（7.5ng/h；6d）增加了雌性LAB大鼠而非雄性LAB大鼠的焦虑相关行为。根据强迫游泳测试的评估，OXT 系统的急性或慢性操作均不会改变抑郁相关行为。综合起来，这些结果表明，对大脑 OXT 系统进行药理学操作可有效减轻精神病理性焦虑动物模型中特质焦虑的极端程度。此外，数据表明，HAB 和 LAB 大鼠之间大脑 OXT 系统活动的差异可能（至少部分）有助于对抗焦虑，但不会导致抑郁相关行为。
Central oxytocin (OXT) has been shown to promote numerous social behaviours, to attenuate hormonal stress responsiveness of the HPA axis and to decrease anxiety. Wistar rats selectively bred for high (HAB) and low (LAB) anxiety-related behaviour, respectively, have been shown to represent a suitable animal model to study the underlying aetiology of psychopathologies like anxiety- and depression-related disorders. The goal of the present studies was to assess the effects of central OXT on anxiety- and depression-related behaviour in male and female HAB and LAB rats. Acute icv OXT (1 μg) or OXT receptor antagonist (OXT-A; 0.75 μg) administration did not affect anxiety-related behaviour in male or female HAB and LAB rats as assessed in the light–dark box. In contrast, chronic icv OXT infusion (10 ng/h; 6 d) attenuated the high level of anxiety-related behaviour in female, but not male, HAB rats, whereas chronic OXT-A infusion (7.5 ng/h; 6 d) increased anxiety-related behaviour in female, but not male, LAB rats. Neither acute nor chronic manipulation of the OXT system altered depression-related behaviour as assessed by the forced swim test. Combined, these results suggest that pharmacological manipulation of the brain OXT system is effective to attenuate extremes in trait anxiety in an animal model of psychopathological anxiety. Moreover, the data indicate that differences in the activity of the brain OXT systems between HAB and LAB rats may, at least partially, contribute to the opposing anxiety but not depression-related behaviour.