Background: Alcohol misuse and post-traumatic stress disorder (PTSD) are highly comorbid, and treatment outcomes are worse in individuals with both conditions. Although more men report experiencing traumatic events than women, the lifetime prevalence of PTSD is twice as high in females. Despite these data trends in humans, preclinical studies of traumatic stress reactivity have been performed almost exclusively in male animals. Methods: This study was designed to examine sex differences in traumatic stress reactivity in alcohol-naive rats (experiment 1) and rats given intermittent access to 20% ethanol in a 2-bottle choice paradigm for 5 weeks (experiment 2). Animals were exposed to predator odor (bobcat urine) and tested for contextual avoidance 24 h later; unstressed controls were never exposed to predator odor. We evaluated changes in physiological arousal using the acoustic startle response (ASR) test at day 2 post-stress and anxiety-like behavior measured in the elevated plus-maze (EPM) at day 17 post-stress. In experiment 3, time course of corticosterone response was examined in male and female rats following exposure to predator odor stress. Results: Alcohol-naive males and females exposed to predator odor displayed blunted weight gain 24 h post-stress, but only a subset of stressed animals exhibited avoidance behavior. In alcohol-drinking animals, the proportion of avoiders was higher in males than females, and predator odor exposure increased ASR in males only. Stressed females exhibited blunted ASR relative to unstressed females and stressed males, regardless of alcohol drinking history. Alcohol-experienced females presented lower anxiety-like behavior and higher general activity in the EPM in comparison with alcohol-experienced males. Plasma corticosterone levels were higher in females immediately after predator odor exposure until 60 min post-stress relative to males. Conclusions: We report robust sex differences in behavioral and endocrine responses to bobcat urine exposure in adult Wistar rats. Also, males with a history of chronic moderate alcohol drinking exhibited increased traumatic stress reactivity relative to alcohol-drinking females. Our findings emphasize the importance of considering sex as a biological variable in the investigation of traumatic stress effects on physiology and behavior.

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Background: Alcohol misuse and post-traumatic stress disorder (PTSD) are highly comorbid and treatment outcomes are worse in individuals with both conditions. Although more men report experiencing traumatic events than women, the lifetime prevalence of PTSD is twice as high in females. Despite these data trends in humans, preclinical studies of traumatic stress reactivity have been performed almost exclusively in male animals. Methods:This study was designed to examine sex differences in traumatic stress reactivity in alcohol-naïve rats and rats given intermittent access to 20% ethanol in a 2-bottle choice paradigm for 5 weeks. Rats were exposed to predator odor (bobcat urine) and tested for avoidance of the odor-paired context 24 hours later; unstressed Controls were never exposed to odor. Two days after stress, we measured physiological arousal using the acoustic startle response (ASR) test. We also measured anxiety-like behavior using the elevated plus-maze (EPM) and circulating corticosterone levels before and immediately after odor exposure. Results:Male and female rats exposed to predator odor displayed blunted weight gain 24 hours post-stress, but only a subset of stressed animals exhibited avoidance behavior. Chronic intermittent alcohol drinking increased the proportion of Avoiders in males and predator odor exposure increased ASR in these animals. Predator odor stress reduced ASR in females relative to unstressed females and stressed males, regardless of alcohol drinking history. Bobcat urine exposure did not promote persistent anxiety-like behavior, but alcohol-experienced males exhibited reduced activity in the EPM in comparison to alcohol-experienced females.3 Furthermore, predator odor increased circulating corticosterone levels in females relative to males and baseline. Conclusions:We report robust sex differences in behavioral and endocrine responses to bobcat urine exposure in adult Wistar rats. Also, chronic moderate alcohol drinking increased traumatic stress reactivity in males but not females. Our findings emphasize the importance of considering sex as a biological variable in the investigation of traumatic stress effects on physiology and behavior. BackgroundPost-traumatic stress disorder (PTSD) is a chronic psychiatric disease that is seen in some but not all individuals after experiencing a life-threatening traumatic event. Major diagnostic criteria for PTSD include re-experiencing the traumatic event, negative affective state, exaggerated startle responses and persistent avoidance of trauma-related cues [1]. Women are twice as likely to develop PTSD after trauma [2, 3] and women with trauma exposure and/or PTSD exhibit more sensitivity to and less tolerance of negative emotions [4,5].Alcohol use disorder (AUD) is one of the most common co-occurring conditions among individuals diagnosed with PTSD [6,7]. Approximately one-third of individuals with lifetime PTSD also meet criteria for AUD [8]. Some populations, such as military personnel, are at high risk for AUD and PTSD comorbidities. For...