Perry Thomas W, Carvour Harrison M, Reichert Amanda N, Sneddon Elizabeth A, Roemer Charlotte A E G, Gao Ying Ying, Schuh Kristen M, Shand Natalie A, Quinn Jennifer J, Radke Anna K
Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA.
bioRxiv. 2024 Aug 24:2023.01.21.524642. doi: 10.1101/2023.01.21.524642.
In humans, early life stress (ELS) is associated with an increased risk for developing both alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD). We previously used an infant footshock model that produces stress-enhanced fear learning (SEFL) in rats and mice and increases aversion-resistant alcohol drinking in rats to explore this shared predisposition. The goal of the current study was to extend this model of comorbid PTSD and AUD to male and female C57BL/6J mice.
Acute ELS was induced using 15 footshocks on postnatal day (PND) 17. In adulthood, alcohol drinking behavior was tested in one of three two-bottle choice drinking paradigms. In continuous access, mice were given 24 h access to 5% or 10% ethanol and water for five consecutive drinking sessions each. In limited access drinking in the dark, mice were given 2 h of access to 15% ethanol and water across 15 sessions 3 h into the dark cycle. In intermittent access, mice were presented with 20% ethanol and water Monday, Wednesday, and Friday, for four consecutive weeks. In a fifth week of intermittent access drinking, increasing concentrations of quinine (10 mg/L, 100 mg/L, and 200 mg/L) were added to the ethanol to test aversion-resistant drinking. Intermittent access drinking was tested with and without a period of adolescent drinking (PND 35).
Infant footshock did not alter drinking in the continuous or limited access tasks. Adult consumption and preference were lower in the intermittent access task when adolescent drinking was included and there were ELS-induced differences in consumption of quinine-adulterated ethanol in females.
Our results demonstrate that infant footshock followed by a period of adolescent drinking is a viable model of comorbid PTSD and AUD in rats and mice.
在人类中，早年生活应激（ELS）与酒精使用障碍（AUD）和创伤后应激障碍（PTSD）的发病风险增加有关。我们之前使用了一种幼鼠足部电击模型，该模型可在大鼠和小鼠中产生应激增强的恐惧学习（SEFL），并增加大鼠对厌恶的酒精的饮用量，以探索这种共同的易感性。本研究的目的是将这种PTSD和AUD共病模型扩展到雄性和雌性C57BL/6J小鼠。
在出生后第17天（PND 17）使用15次足部电击诱导急性ELS。成年后，在三种双瓶选择饮水范式之一中测试酒精饮用行为。在持续获取模式下，小鼠连续五个饮水时段可随时获取5%或10%的乙醇和水，为期24小时。在黑暗中限时获取模式下，在黑暗周期开始3小时后，小鼠在15个时段中，每次有2小时可获取15%的乙醇和水。在间歇性获取模式下，小鼠在周一、周三和周五可获取20%的乙醇和水，持续四周。在间歇性获取饮水的第五周，向乙醇中添加浓度逐渐增加的奎宁（10毫克/升、100毫克/升和200毫克/升），以测试对厌恶的酒精的饮用情况。间歇性获取饮水在有或没有一段青春期饮酒（PND 35）的情况下进行测试。
幼鼠足部电击并未改变持续获取或限时获取任务中的饮水情况。当包括青春期饮酒时，间歇性获取任务中的成年小鼠摄入量和偏好较低，并且在雌性小鼠中，ELS会导致奎宁掺杂乙醇摄入量的差异。
我们的结果表明，幼鼠足部电击后经历一段青春期饮酒是大鼠和小鼠中PTSD和AUD共病的可行模型。
