Department of Pharmacology, Medical School, University of Athens, 75 Mikras Asias Street, 11527 Goudi, Athens, Greece.
Neuropharmacology. 2012 Jan;62(1):436-45. doi: 10.1016/j.neuropharm.2011.08.025. Epub 2011 Aug 25.
Anxiety and depression are considered as stress-related disorders, which present considerable sex differentiation. In animal models of anxiety and depression sex differences have been described and linked to the sexually dimorphic hypothalamus-pituitary-adrenals (HPA) axis. The present study aimed to adjust corticosterone, the main HPA axis stress hormone, in male and female adrenalectomized rats with oral (25 μg/ml) corticosterone replacement (ADXR). Subsequently we investigated the behavioral performance of ADXR rats in the open field, light/dark and forced swim test (FST). Male ADXR rats showed less anxiety-like behavior when compared to sham-operated controls, despite adequate corticosterone replacement. They further showed increased swimming and reduced climbing behavior in the FST, while immobility duration did not differ from sham-operated males. On the contrary, adrenalectomy and corticosterone replacement did not have significant effects on the female behavioral response. Females were generally more active and presented less anxiety-like behavior than males, while they exhibited higher depressive-like symptomatology in the FST. ADXR affected behavioral responses predominantly in males, which in turn modified sex differences in the behavioral profile. Females in proestrous and estrous did not differ from females in diestrous and methestrous in any measured behavioral response. Present results suggest that the male and not the female behavioral responses in models of anxiety and depression were mainly affected by ADXR. These findings may play a significant role in explaining the differential coping strategy of the two sexes in response to stressful experiences. This article is part of a Special Issue entitled 'Anxiety and Depression'.
焦虑和抑郁被认为是与应激相关的疾病，它们表现出相当大的性别差异。在焦虑和抑郁的动物模型中已经描述了性别差异，并与性二态下丘脑-垂体-肾上腺（HPA）轴相关联。本研究旨在通过口服（25μg/ml）皮质酮替代物（ADXR）来调整雄性和雌性肾上腺切除大鼠的皮质酮，这是 HPA 轴的主要应激激素。随后，我们在旷场、明暗和强迫游泳试验（FST）中研究了 ADXR 大鼠的行为表现。与假手术对照组相比，雄性 ADXR 大鼠表现出较少的焦虑样行为，尽管皮质酮替代充足。它们在 FST 中进一步表现出游泳增加和攀爬减少，而不动时间与假手术雄性没有差异。相反，肾上腺切除术和皮质酮替代对雌性的行为反应没有显著影响。女性通常比男性更活跃，表现出较少的焦虑样行为，而在 FST 中表现出更高的抑郁样症状。ADXR 主要影响雄性的行为反应，从而改变了行为特征中的性别差异。发情前期和发情期的雌性与发情后期和间情期的雌性在任何测量的行为反应中均无差异。目前的结果表明，ADXR 主要影响焦虑和抑郁模型中雄性而不是雌性的行为反应。这些发现可能在解释两性在应激反应中不同的应对策略方面发挥重要作用。本文是题为“焦虑和抑郁”的特刊的一部分。
