Post-traumatic stress disorder (PTSD) is one of the most prevalent co-occurring psychiatric pathologies among individuals with alcohol use disorder (AUD). Although comorbidity worsens the symptoms and prognosis following treatment of both disorders, no approved compound has demonstrated efficacy to treat AUD comorbid with PTSD. GABAergic neurosteroids are altered by chronic alcohol and play a role in the stress and arousal systems degraded in PTSD. Particularly, dampened plasma levels of allopregnanolone are found in individuals with alcohol dependence or undergoing alcohol withdrawal and individuals with PTSD. Our goal was to establish an animal model to explore the role that neurosteroid levels have in predicting drinking or stress reactivity in individuals exposed to social defeat. Male and female CFW mice were trained to aggress C57BL/6J intruders. Intruder mice received ten social defeat experiences with sex-matched aggressors. Blood samples were taken following the first defeat. Following chronic social defeat, mice were given limited access to alcohol (20%, v/v) 3 hours a day for 14 days to assess changes in the escalation of binge drinking for intruder mice and non-stressed controls. After a withdrawal period, tissue was harvested to assess neuronal response to stress or acute alcohol, using c-Fos immunoreactivity. Behaviors and images were coded by experimenters blinded to treatment groups. Future work will determine if these mice show variability in the effect that chronic stress has on binge drinking behavior and whether this variability may be predicted by changes in circulating neurosteroid levels in both males and females experiencing chronic stress.
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