研究 DBA/2J 小鼠运动性对乙醇的敏感性与 PTSD 样簇之间的相互关系。
Investigating the reciprocal relationships between locomotor sensitization to ethanol and PTSD-like clusters in DBA/2J mice.
机构信息
Psychology & Neuroscience of Cognition - PsyNCogn, Liège University, Belgium; Laboratory of Neurophysiology, GIGA Neurosciences, all at Liège University, B-4000, Sart Tilman, Liège, Belgium; Département de psychiatrie, Faculté de médecine, Université de Kinshasa, Democratic Republic of the Congo.
Psychology & Neuroscience of Cognition - PsyNCogn, Liège University, Belgium.
出版信息
Behav Brain Res. 2019 Aug 5;368:111909. doi: 10.1016/j.bbr.2019.111909. Epub 2019 Apr 12.
BACKGROUND
Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are two conditions that co-occur frequently. The mechanistic explanations of this co-morbidity are still unclear. The goal of this study was twofold. First to investigate whether PTSD reduces the threshold for the acquisition of ethanol sensitization in an animal model of PTSD. Then to investigate whether ethanol sensitization modulates the expression of PTSD.
METHODS
152 female inbred DBA/2 J mice were submitted to an inescapable footshock paradigm to induce a PTSD-like condition (PTSDLC) and to a paradigm of locomotor sensitization to ethanol. In a first experiment, mice were submitted to the PTSDLC and then repeatedly injected with either saline, 1 g/kg ethanol or 2 g/kg ethanol. Their sensitization to the locomotor stimulant effects of ethanol was then tested in an open field. In a second experiment, mice were first sensitized to the locomotor stimulant effects of ethanol and then tested for their behavioral response to PTSDLC.
RESULTS
In the first experiment, PTSDLC failed to induce a significant locomotor sensitization at the subthreshold dose of 1 g/kg ethanol. However, with 2 g/kg ethanol, a stronger ethanol sensitization was observed in mice submitted to the footshock relative to the control group. In the second experiment, ethanol sensitization increased only some of the behavioral clusters of PTSDLC, namely the fear generalization in a new context.
CONCLUSION
PTSDLC did not reduce the dose threshold for the acquisition of ethanol sensitization but strengthened the development of ethanol sensitization with effective doses. This suggests that PTSD might interact with one of the mechanisms underlying the development of alcohol sensitization. When the relationship between ethanol sensitization and PTSDLC is tested in the reverse direction, the present study only shows a significant effect of ethanol administration on the "sensitized fear" PTSD cluster.
背景
创伤后应激障碍（PTSD）和酒精使用障碍（AUD）是两种经常同时发生的疾病。这种共病的机制解释仍不清楚。本研究的目的有两个。首先，研究 PTSD 是否会降低动物 PTSD 模型中乙醇敏化获得的阈值。然后，研究乙醇敏化是否会调节 PTSD 的表达。
方法
152 只雌性近交系 DBA/2J 小鼠接受不可逃避的足底电击范式以诱导 PTSD 样条件（PTSDLC）和乙醇的运动敏化范式。在第一个实验中，小鼠先接受 PTSDLC，然后反复注射生理盐水、1g/kg 乙醇或 2g/kg 乙醇。然后在一个开阔场中测试它们对乙醇运动兴奋剂作用的敏化作用。在第二个实验中，小鼠首先对乙醇的运动兴奋剂作用产生敏化作用，然后测试它们对 PTSDLC 的行为反应。
结果
在第一个实验中，PTSDLC 未能在 1g/kg 乙醇的亚阈值剂量下引起明显的运动敏化作用。然而，在给予 2g/kg 乙醇时，与对照组相比，在接受足底电击的小鼠中观察到更强的乙醇敏化作用。在第二个实验中，乙醇敏化作用仅增加了 PTSDLC 的一些行为群集，即新环境中的恐惧泛化。
结论
PTSDLC 并未降低获得乙醇敏化作用的剂量阈值，但有效剂量下增强了乙醇敏化作用的发展。这表明 PTSD 可能与酒精敏化作用发展的机制之一相互作用。当在相反方向上测试乙醇敏化作用和 PTSDLC 之间的关系时，本研究仅显示出乙醇给药对“敏化恐惧”PTSD 簇有显著影响。
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