Sex differences in traumatic stress reactivity of rats with a history of alcohol drinking

Abstract

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...

Exposure to the predator odor TMT induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats

“…Sex differences in response to predator odor are documented 60 and women suffer from PTSD at three times the rate of men 3,16 . Therefore, future work should examine sex differences in response to TMT stress.…”