Enduring sensorimotor gating abnormalities following predator exposure or corticotropin-releasing factor in rats: a model for PTSD-like information-processing deficits?
Enduring sensorimotor gating abnormalities following predator exposure or corticotropin-releasing factor in rats: a model for PTSD-like information-processing deficits?
复制标题
DOI：
10.1016/j.neuropharm.2011.01.040
复制
发表时间：
2012-02
影响因子：
4.7
通讯作者：
Connors, Elenora E.
中科院分区：
文献类型：
--
作者：
Bakshi, Vaishali P.;Alsene, Karen M.;Roseboom, Patrick H.;Connors, Elenora E.
前脉冲抑制（PPI）的缺陷可能是临床观察到的创伤后应激障碍（PTSD）的特征之一，在急性创伤事件结束后很长时间才出现。因此，PPI降低可能代表了某些患者这种疾病的持久心理生理学标志。PPI是感觉运动门控的一种操作措施，是指在强烈的惊吓刺激之前立即出现的弱刺激抑制随后惊吓反应的幅度的现象。压力对PPI的影响一直相对研究不足，特别是，很少有关于行为学相关的心理压力对PPI影响的信息。我们的目的是开发一个范例，通过比较一个纯粹的心理应激（捕食者暴露）的影响，疼痛性的物理应激（电击脚）对PPI和基线惊吓反应在大鼠在一段时间后的压力介绍的压力诱导的感觉运动门控异常。将雄性Sprague-Dawley大鼠暴露于雪貂（在保护笼内）5分钟或留在其家中，然后在暴露后立即、24小时、48小时和9天检测PPI。在一组单独的大鼠中评价足电击的影响。将应激呈现所观察到的效应与促肾上腺皮质激素释放因子（CRF; 0.5和3μg/6μl，脑室内）引起的效应进行比较。最后，这些压力和CRF管理对血浆皮质酮的影响进行了测量。PPI被破坏后24小时雪貂曝光，相比之下，足电击未能影响PPI在任何时候。CRF模仿捕食者应激特征，低剂量在输注后24小时产生PPI缺陷。有趣的是，高剂量在输注后24小时也产生了PPI缺陷，但在该剂量下，PPI缺陷甚至在9天后也很明显。血浆皮质酮水平升高急性（PPI赤字出现之前）的压力和CRF，但恢复到正常对照水平24小时后，当PPI赤字。因此，捕食者暴露产生延迟破坏PPI，和CRF受体的刺激重演这些影响。同时HPA轴激活既不是必要的，也不是充分的这些PPI赤字。这些结果表明，捕食者暴露，也许通过CRF，可以模拟延迟发作和持续的感觉运动门控异常，已在临床上观察到的创伤后应激障碍，并使用该模型的进一步研究可能会揭示在这种疾病的机制信息处理缺陷。
A deficit in prepulse inhibition (PPI) can be one of the clinically observed features of post traumatic stress disorder (PTSD) that is seen long after the acute traumatic episode has terminated. Thus, reduced PPI may represent an enduring psychophysiological marker of this illness in some patients. PPI is an operational measure of sensorimotor gating and refers to the phenomenon in which a weak stimulus presented immediately before an intense startling stimulus inhibits the magnitude of the subsequent startle response. The effects of stress on PPI have been relatively understudied, and in particular, there is very little information on PPI effects of ethologically relevant psychological stressors. We aimed to develop a paradigm for evaluating stress-induced sensorimotor gating abnormalities by comparing the effects of a purely psychological stressor (predator exposure) to those of a noiciceptive physical stressor (footshock) on PPI and baseline startle responses in rats over an extended period of time following stressor presentation. Male Sprague-Dawley rats were exposed (within a protective cage) to ferrets for 5 min or left in their homecage and then tested for PPI immediately, 24h, 48h, and 9 days after the exposure. The effects of footshock were evaluated in a separate set of rats. The effects seen with stressor presentation were compared to that elicited by corticotropin-releasing factor (CRF; 0.5 and 3μg/6μl, intracerebroventricularly). Finally, the effects of these stressors and CRF administration on plasma corticosterone were measured. PPI was disrupted 24h after ferret exposure; in contrast, footshock failed to affect PPI at any time. CRF mimicked the predator stress profile, with the low dose producing a PPI deficit 24h after infusion. Interestingly, the high dose also produced a PPI deficit 24h after infusion, but with this dose, the PPI deficit was evident even 9d later. Plasma corticosterone levels were elevated acutely (before PPI deficits emerged) by both stressors and CRF, but returned to normal control levels 24h later, when PPI deficits were present. Thus, predator exposure produces a delayed disruption of PPI, and stimulation of CRF receptors recapitulates these effects. Contemporaneous HPA axis activation is neither necessary nor sufficient for these PPI deficits. These results indicate that predator exposure, perhaps acting through CRF, may model the delayed-onset and persistent sensorimotor gating abnormalities that have been observed clinically in PTSD, and that further studies using this model may shed insight on the mechanisms information-processing deficits in this disorder.
登录
查看更多内容
在大鼠和人类中持续的恐惧：恐惧与焦虑中的杏仁核的作用。
DOI：
10.1038/npp.2009.109
发表时间：
2010-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.6
作者：
Cohen, H;Zohar, J;Matar, M
通讯作者：
Matar, M
影响因子：
5
作者：
Conti, LH
通讯作者：
Conti, LH
影响因子：
2.5
作者：
Aston-Jones, G;Cohen, JD
通讯作者：
Cohen, JD
影响因子：
11.3
作者：
Betensky, Julia D.;Robinson, Delbert G.;Szeszko, Philip R.
通讯作者：
Szeszko, Philip R.