Piggott Veronica M, Lloyd Scott C, Perrine Shane A, Conti Alana C
Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI, United States.
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States.
Front Behav Neurosci. 2020 Jun 30;14:114. doi: 10.3389/fnbeh.2020.00114. eCollection 2020.
Individuals with post-traumatic stress disorder (PTSD) often use alcohol to cope with their distress. This aberrant use of alcohol often develops into alcohol use disorder (AUD) leading to high rates of PTSD-AUD co-occurrence. Individuals with comorbid PTSD-AUD have more intense alcohol cravings and increased relapse rates during withdrawal than those with AUD alone. Also, individuals with PTSD or AUD alone often show similar psychological behaviors, such as impulsivity and anhedonia. Extensive clinical studies on the behavioral effects of PTSD-AUD comorbidity, namely alcohol use, have been performed. However, these effects have not been well studied or mechanistically explored in animal models. Therefore, the present study evaluated the effects of traumatic stress comorbid with alcohol exposures on ethanol intake, impulsivity, and anhedonia in mice. Adult male C57Bl/6 mice were first exposed to either mouse single-prolonged stress (mSPS), an animal model that has been validated for characteristics akin to PTSD symptoms, or control conditions. Baseline two-bottle choice ethanol consumption and preference tests were conducted after a 7-day isolation period, as part of the mSPS exposure. Next, mice were exposed to air or chronic intermittent ethanol (CIE), a vapor-induced ethanol dependence and withdrawal model, for 4 weeks. Two-bottle choice ethanol drinking was used to measure dependence-induced ethanol consumption and preference during periods intervening CIE cycles. The novelty suppressed feeding (NSF) test was used to evaluate impulsivity and anhedonia behaviors 48 h after mSPS and/or repeated CIE exposure. Results showed that, compared to control conditions, mSPS did not affect baseline ethanol consumption and preference. However, mSPS-CIE mice increased Post-CIE ethanol consumption compared to Control-Air mice. Mice exposed to mSPS had a shorter latency to feed during the NSF, whereas CIE-exposed mice consumed less palatable food reward in their home cage after the NSF. These results demonstrate that mice exposed to both mSPS and CIE are more vulnerable to ethanol withdrawal effects, and those exposed to mSPS have increased impulsivity, while CIE exposure increases anhedonia. Future studies to examine the relationship between behavioral outcomes and the molecular mechanisms in the brain after PTSD-AUD are warranted.
创伤后应激障碍（PTSD）患者常借助酒精来应对自身的痛苦。这种异常的酒精使用往往会发展为酒精使用障碍（AUD），导致PTSD与AUD的共病率很高。与单纯患有AUD的个体相比，患有PTSD - AUD共病的个体在戒酒期间对酒精的渴望更强烈，复发率也更高。此外，单独患有PTSD或AUD的个体通常表现出相似的心理行为，如冲动性和快感缺失。关于PTSD - AUD共病的行为影响，即酒精使用，已经进行了广泛的临床研究。然而，在动物模型中，这些影响尚未得到充分研究或机制探索。因此，本研究评估了与酒精暴露共病的创伤应激对小鼠乙醇摄入量、冲动性和快感缺失的影响。成年雄性C57Bl/6小鼠首先暴露于小鼠单次长时间应激（mSPS），这是一种已被验证具有类似于PTSD症状特征的动物模型，或者暴露于对照条件下。作为mSPS暴露的一部分，在7天的隔离期后进行基线双瓶选择乙醇消耗和偏好测试。接下来，将小鼠暴露于空气或慢性间歇性乙醇（CIE）中4周，CIE是一种通过蒸汽诱导乙醇依赖和戒断的模型。在CIE周期之间的时间段内，使用双瓶选择乙醇饮用测试来测量依赖诱导的乙醇消耗和偏好。在mSPS和/或重复CIE暴露后48小时，使用新奇抑制摄食（NSF）测试来评估冲动性和快感缺失行为。结果表明，与对照条件相比，mSPS不影响基线乙醇消耗和偏好。然而，与对照 - 空气组小鼠相比，mSPS - CIE组小鼠在CIE后乙醇消耗量增加。暴露于mSPS的小鼠在NSF期间摄食潜伏期更短，而暴露于CIE的小鼠在NSF后在其笼舍中消耗的美味食物奖励更少。这些结果表明，同时暴露于mSPS和CIE的小鼠更容易受到乙醇戒断效应的影响，暴露于mSPS的小鼠冲动性增加，而暴露于CIE的小鼠快感缺失增加。未来有必要开展研究，以探究PTSD - AUD后行为结果与大脑分子机制之间的关系。
