Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX, USA.
Institute for Neuroscience, Texas A&M University, College Station, TX, USA.
Psychoneuroendocrinology. 2022 Jul;141:105776. doi: 10.1016/j.psyneuen.2022.105776. Epub 2022 Apr 26.
The increased susceptibility of women to stress and trauma-related disorders compared to men suggests a role for ovarian hormones in modulating fear and anxiety. In both humans and rodents, estrogen and progesterone have been shown to influence fear learning during acquisition, expression, and extinction. Recently, we showed that allopregnanolone (ALLO), a progesterone (PROG) metabolite and GABA receptor potentiator, confers state-dependent contextual fear when infused into the bed nucleus of the stria terminalis of male rats. In order to determine whether estrous cycle-related fluctuations in circulating PROG confer state-dependent contextual fear in female rats, animals received Pavlovian fear conditioning during an estrous cycle phase when PROG was either low (late diestrus) or high (late proestrus). After conditioning, animals were tested for contextual fear in either the same or different estrous cycle phase. Subjects conditioned in diestrus and tested in proestrus showed lower levels of contextual fear compared to subjects conditioned and tested in the same estrous cycle phase (either diestrus or proestrus), suggesting a state-dependent effect of estrous cycle phase on fear learning. This state dependence was asymmetric, however, as animals trained in proestrus and tested in diestrus exhibited high levels of contextual fear. In ovariectomized (OVX) females treated acutely with either PROG or vehicle, state dependence was not observed. These results suggest that the hormonal state in diestrus may play a role in conferring state dependence to conditioned fear in naturally cycling female rats but not in an OVX model.
与男性相比，女性更容易受到压力和与创伤相关的疾病的影响，这表明卵巢激素在调节恐惧和焦虑方面发挥作用。在人类和啮齿动物中，雌激素和孕激素已被证明会影响获得、表达和消除过程中的恐惧学习。最近，我们表明，孕酮（PROG）代谢物和 GABA 受体增强剂别孕烯醇酮（ALLO）在雄性大鼠终纹床核内输注时会赋予状态依赖的情境性恐惧。为了确定循环 PROG 中的发情周期相关波动是否会赋予雌性大鼠状态依赖的情境性恐惧，动物在 PROG 水平较低（发情后期）或较高（发情前期）的发情周期阶段接受了条件恐惧训练。在条件作用后，动物在相同或不同发情周期阶段进行情境恐惧测试。在发情后期进行条件作用并在发情前期进行测试的动物与在相同发情周期阶段（发情后期或发情前期）进行条件作用和测试的动物相比，表现出较低水平的情境恐惧，这表明发情周期阶段对恐惧学习有状态依赖性影响。然而，这种状态依赖性是不对称的，因为在发情前期进行训练并在发情后期进行测试的动物表现出高水平的情境恐惧。在急性接受 PROG 或载体处理的卵巢切除（OVX）雌性动物中，没有观察到状态依赖性。这些结果表明，发情后期的激素状态可能在赋予自然发情周期雌性大鼠条件恐惧的状态依赖性方面发挥作用，但在 OVX 模型中则不起作用。
