Abstract

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.

Highlights

  • Post-traumatic stress disorder (PTSD) is a serious mental health disorder that people may develop directly or indirectly after experiencing a traumatic event(s)

  • A Fisher’s LSD post hoc comparison test revealed that the Mouse single-prolonged stress (mSPS)-Chronic Intermittent Ethanol (CIE) (n = 5) group significantly increased their vapor-induced ethanol consumption in Test 1 and continued to consume a similar amount of ethanol in Test 4 compared to the Control-Air (n = 5; p < 0.05), and the Control-CIE groups (n = 4; p < 0.05) in Test 1. mSPS-Air mice (n = 4; p < 0.05) significantly increased their average ethanol consumption compared to the Control-Air group after the first cycle of air

  • The current study evaluated the effects of traumatic stress exposure, chronic alcohol exposure, and co-occurring of both exposures on behavioral outcomes including ethanol intake and preference, impulsivity, and anhedonia

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Summary

Introduction

Post-traumatic stress disorder (PTSD) is a serious mental health disorder that people may develop directly or indirectly after experiencing a traumatic event(s). According to the DSM-5, PTSD symptoms include flashbacks, avoidance behavior of the traumatic event(s), negative mood, and hyperarousal (American Psychiatric Association, 2013). Individuals who are diagnosed with PTSD have an increased propensity (28–85%) to develop alcohol use disorder (AUD; Kessler et al, 1995; Baker et al, 2009; Ralevski et al, 2014). Characteristics of AUD include high tolerance to short-term effects of ethanol and vulnerability to withdrawal symptoms, such as anhedonia, during alcohol abstinence (Becker, 2008; Martinotti et al, 2008; Hatzigiakoumis et al, 2011; Pava and Woodward, 2012). Individuals with comorbid PTSD and AUD have more intense alcohol cravings and relapse more frequently during withdrawal than those with AUD only (Brown et al, 1999; Ouimette et al, 1999; Berenz et al, 2017), suggesting that the comorbid disorder is unique from either condition alone

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