Effects of pregabalin on neurobehavior in an adult male rat model of PTSD

Posttraumatic stress disorder (PTSD) can be a very debilitating condition. Effective approaches to prevent and treat PTSD are important areas of basic science research. Pregabalin (PGB), a gabapentinoid derivative of γ-aminobutyric acid, possesses the potential to positively affect neurobehavioral changes associated with PTSD. Using a rodent model of PTSD, the aims of this study were to determine the effects of PGB as a possible prevention for the development of PTSD-like symptoms and its use as a possible treatment. A prospective, experimental, between groups design was used in conjunction with a three-day restraint/shock PTSD stress model. Sixty rats were randomly assigned between two groups, non-stressed and stressed (PTSD). Each of the main two groups was then randomly assigned into six experimental groups: control vehicle, control PGB, control naïve, PTSD vehicle, PTSD Pre-PGB (prophylactic), PTSD Post-PGB (non-prophylactic). The neurobehavioral components of PTSD were evaluated using the elevated plus maze (EPM), Morris water maze (MWM), and forced swim test (FST). Pregabalin administered 24 hours before the initial PTSD event or for 10 days following the last PTSD stress event did not statistically improve mean open arm exploration on the EPM, spatial memory, and learning in the MWM or behavioral despair measured by the FST (p > 0.05).

创伤后应激障碍（Posttraumatic stress disorder, PTSD）是一种极具致残性的精神病症，其有效防治手段是基础科学研究的重要领域。普瑞巴林（Pregabalin, PGB）作为γ-氨基丁酸（γ-aminobutyric acid）的加巴喷丁类衍生物，具备改善与创伤后应激障碍相关的神经行为改变的潜力。本研究采用创伤后应激障碍啮齿动物模型，旨在探究普瑞巴林作为创伤后应激障碍样症状潜在预防手段的效果，以及其作为潜在治疗手段的作用。研究采用前瞻性实验组间设计，结合为期3天的束缚-应激创伤模型开展实验。将60只大鼠随机分为两组：非应激组与应激造模组（PTSD模型组）。随后将两大组再分别随机分为6个实验组：对照溶剂组、对照普瑞巴林组、空白对照组、PTSD模型溶剂组、PTSD模型预防性普瑞巴林给药组（prophylactic）、PTSD模型非预防性普瑞巴林给药组（non-prophylactic）。采用高架十字迷宫（elevated plus maze, EPM）、莫里斯水迷宫（morris water maze, MWM）以及强迫游泳实验（forced swim test, FST）对创伤后应激障碍的神经行为学指标进行评估。结果显示，在初始创伤应激事件发生前24小时给药，或末次创伤应激事件结束后连续给药10天的普瑞巴林，并未在高架十字迷宫的平均开放臂探索时长、莫里斯水迷宫的空间记忆与学习能力，以及强迫游泳实验测得的行为绝望程度等指标上产生统计学意义上的显著改善（p > 0.05）。