Sex differences in traumatic stress reactivity in rats with and without a history of alcohol drinking

Lucas Albrechet-Souza,Connor L. Schratz,Nicholas W. Gilpin

doi:10.1186/s13293-020-00303-w

Abstract

BackgroundAlcohol 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.MethodsThis 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.ResultsAlcohol-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.ConclusionsWe 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.

Highlights

Alcohol misuse and post-traumatic stress disorder (PTSD) are highly comorbid, and treatment outcomes are worse in individuals with both conditions
To determine whether predator odor (PO) stress affected startle reactivity differently in male and female rats with a history of alcohol drinking, acoustic startle response (ASR) data were analyzed for each decibel
Males and females exposed to PO displayed blunted weight gain 24 h post-stress, but only a subset of stressed animals exhibited avoidance behavior

Summary

Introduction

Alcohol misuse and post-traumatic stress disorder (PTSD) are highly comorbid, and treatment outcomes are worse in individuals with both conditions. 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. Post-traumatic stress disorder (PTSD) is a chronic psychiatric disease that is seen in some but not all individuals after experiencing a traumatic event. One third of individuals with lifetime PTSD meet the criteria for AUD [8]. Men have a higher prevalence of AUD than women, and women have a higher prevalence of PTSD than men, any individual with either disorder is more likely to have the other [10]

Methods

Results

Discussion

Conclusion