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, Ohio, USA.
Alcohol Clin Exp Res (Hoboken). 2025 Mar;49(3):678-691. doi: 10.1111/acer.70004. Epub 2025 Jan 31.
In humans, early life stress (ELS) is associated with an increased risk for developing both alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). We previously used an infant footshock model in rats that produces stress-enhanced fear learning (SEFL) and increases aversion-resistant alcohol drinking to explore this shared predisposition. The goal of the current study was to test the viability of this procedure as a model of comorbid PTSD and AUD in 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% and 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, 100, 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. In the intermittent access task, adult consumption and preference were lower in shocked mice when adolescent drinking was included. Aversion resistance was greater in females following infant footshock and adolescent drinking.
Our results demonstrate that ELS, in the form of infant footshock on PND 17, must be followed by a period of adolescent drinking to affect adult alcohol consumption in 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。我们之前在大鼠中使用婴儿足部电击模型,该模型会产生应激增强的恐惧学习(SEFL)并增加抗厌恶饮酒行为,以探究这种共同的易感性。本研究的目的是测试该程序作为雄性和雌性C57BL/6J小鼠共病PTSD和AUD模型的可行性。
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,在三种双瓶选择饮酒范式之一中测试饮酒行为。在持续获取模式下,小鼠连续五个饮酒时段每天有24小时获取5%和10%乙醇及水的机会。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个时段内有2小时获取15%乙醇及水的机会。在间歇性获取模式下,小鼠在周一、周三和周五接触20%乙醇及水,持续四周。在间歇性获取饮酒的第五周,向乙醇中添加浓度逐渐增加的奎宁(10、100和200mg/L)以测试抗厌恶饮酒行为。间歇性获取饮酒在有或没有青春期饮酒阶段(PND 35)的情况下进行测试。
婴儿足部电击并未改变持续或限时获取任务中的饮酒情况。在间歇性获取任务中,当包括青春期饮酒时,受电击小鼠的成年期饮酒量和偏好较低。婴儿足部电击和青春期饮酒后,雌性小鼠的抗厌恶能力更强。
我们的结果表明,以PND 17时的婴儿足部电击形式存在的ELS,必须继之以一段时间的青春期饮酒,才能影响小鼠的成年期酒精摄入量。