Pallarès M, Llidó A, Mòdol L, Vallée M, Darbra S
Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, Edifici B, campus UAB, 08193 Bellaterra, Barcelona, Spain.
Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, Edifici B, campus UAB, 08193 Bellaterra, Barcelona, Spain.
Behav Brain Res. 2015 Aug 1;289:55-60. doi: 10.1016/j.bbr.2015.04.023. Epub 2015 Apr 22.
Acute stress has been demonstrated to alter sensory gating processes, measured by the prepulse inhibition of the startle response (PPI). It is well known that brain and plasma levels of the neurosteroid allopregnanolone (ALLO) increase after acute environmental stress, fact that has been considered a homeostatic mechanism in restoring normal function following stress. Thus, it is of great interest to study the contribution of stress-altered plasma ALLO levels on PPI function. For this purpose, animals were injected with finasteride, an ALLO synthesis inhibitor, and submitted to swim stress before PPI testing. In order to obtain ALLO plasma levels, a separate set of animals that followed the same experimental procedure was used. We hypothesize that the blockade of ALLO production in response to stress can increase the stress-induced PPI disruption. In accordance with other authors, our results indicate that acute swim stress disrupted the normal PPI evolution (increase) related to the increase in prepulse intensities, and also decreased PPI at the highest prepulse intensity level (15 db above background). Finasteride potentiated the PPI decrease induced by swim stress in the intermediate prepulse intensity (10 db above background). As expected, plasma ALLO levels were increased in stressed animals and this increase was neutralized by prior finasteride administration. These results indicate that the neutralization of the physiological plasma ALLO levels increase after acute stress potentiates stress-induced PPI disruption. This data suggests that alterations in homeostatic ALLO synthesis mechanism may be linked to some neuropsychiatric disorders related to stress, such as anxiety/depression disorders.
急性应激已被证明会改变感觉门控过程，这一过程通过惊吓反应的前脉冲抑制（PPI）来衡量。众所周知，急性环境应激后，神经甾体别孕烯醇酮（ALLO）的脑内和血浆水平会升高，这一事实被认为是应激后恢复正常功能的一种稳态机制。因此，研究应激改变的血浆ALLO水平对PPI功能的影响具有重要意义。为此，在进行PPI测试前，给动物注射了一种ALLO合成抑制剂非那雄胺，并使其遭受游泳应激。为了获得血浆ALLO水平，使用了另一组遵循相同实验程序的动物。我们假设，对应激反应中ALLO产生的阻断会增加应激诱导的PPI破坏。与其他作者一致，我们的结果表明，急性游泳应激破坏了与前脉冲强度增加相关的正常PPI演变（增加），并且在最高前脉冲强度水平（高于背景15分贝）时也降低了PPI。非那雄胺增强了游泳应激在中等前脉冲强度（高于背景10分贝）时诱导的PPI降低。正如预期的那样，应激动物的血浆ALLO水平升高，而这种升高被预先给予的非那雄胺所抵消。这些结果表明，急性应激后生理血浆ALLO水平升高的中和会增强应激诱导的PPI破坏。这些数据表明，稳态ALLO合成机制的改变可能与一些与应激相关的神经精神疾病有关，如焦虑/抑郁障碍。
