Karaoglan Mehmet, Grace Anthony A
Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, United States.
Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, United States.
Psychiatry Res. 2025 Jan;343:116283. doi: 10.1016/j.psychres.2024.116283. Epub 2024 Nov 23.
Post-Traumatic Stress Disorder (PTSD) is a debilitating psychiatric disorder that arises following exposure to an extreme stress. PTSD is characterized by five primary trauma-related symptom clusters, including symptoms of negative mood and hyperresponsivity to the traumatic event. Regrettably, the current therapy options are not highly effective. Therefore, prevention of PTSD is crucial and potentially applicable. Prazosin is an anti-adrenergic medication that is used to reduce nightmares in patient with PTSD, and can also mitigate the noradrenergic dysfunction caused by trauma. Here we show that administration of prazosin prior to the trauma prevented learned helplessness behavior in adult male rats. We show that the animals that were exposed to three days of inescapable foot shocks preceded by prazosin injections have fewer prazosin-treated animals showing learned helplessness compared to saline-treated animals. Nevertheless, there was no significant difference in anxiety-related behavior as measured in the elevated plus maze. Furthermore, the results of in vivo electrophysiological recordings of the ventral tegmental area shows that the prazosin group has a trend of increased number of active dopaminergic cells per track; this is significant when limited to central region of the ventral tegmental area. Our results demonstrate that prazosin has a potential for prevention of PTSD.
创伤后应激障碍（PTSD）是一种使人衰弱的精神障碍，在经历极端压力后出现。PTSD的特征是五个主要的与创伤相关的症状群，包括负面情绪症状和对创伤事件的过度反应。遗憾的是，目前的治疗选择效果并不理想。因此，预防PTSD至关重要且具有潜在的适用性。哌唑嗪是一种抗肾上腺素能药物，用于减少PTSD患者的噩梦，还可以减轻创伤引起的去甲肾上腺素能功能障碍。在这里，我们表明在创伤前给予哌唑嗪可预防成年雄性大鼠的习得性无助行为。我们发现，与生理盐水处理的动物相比，在注射哌唑嗪后遭受三天不可逃避的足部电击的动物中，表现出习得性无助的哌唑嗪处理动物较少。然而，在高架十字迷宫中测量的焦虑相关行为没有显著差异。此外，腹侧被盖区的体内电生理记录结果表明，哌唑嗪组每条轨迹中活跃多巴胺能细胞数量有增加的趋势；当仅限于腹侧被盖区的中央区域时，这一趋势具有显著性。我们的结果表明哌唑嗪具有预防PTSD的潜力。
