Sex and context differences in the effects of trauma on comorbid alcohol use and post‐traumatic stress phenotypes in actively drinking rats

Abstract

Alcohol use disorder (AUD) and affective disorders are frequently comorbid and share underlying mechanisms that could be targets for comprehensive treatment. Posttraumatic stress disorder (PTSD) has high comorbidity with AUD, but comprehensive models of this overlap are nascent. We recently characterized a model of comorbid AUD and PTSD-like symptoms, wherein stressed rats receive an inhibitory avoidance (IA)-related footshock on two occasions followed by two-bottle choice (2BC) voluntary alcohol drinking. Stressed rats received the second footshock in a familiar (FAM, same IA box as the first footshock) or novel context (NOV, single-chambered apparatus); the FAM paradigm more effectively increased alcohol drinking in males and the NOV paradigm in females. During abstinence, stressed males displayed avoidancelike PTSD symptoms, and females showed hyperarousal-like PTSD symptoms. Rats in the model had altered spontaneous action potential-independent GABAergic transmission in the central amygdala (CeA), a brain region key in alcohol dependence and stress-related signaling. However, PTSD sufferers may have alcohol experience prior to their trauma. Here, we therefore modified our AUD/PTSD comorbidity model to provide 3 weeks of intermittent extended alcohol access before footshock and then studied the effects of NOV and FAM stress on drinking and PTSD phenotypes. NOV stress suppressed the escalation of alcohol intake and preference seen in male controls, but no stress effects were seen on drinking in females. Additionally, NOV males had decreased action potential-independent presynaptic GABA release and delayed postsynaptic GABA A receptor kinetics in the CeA compared to control and FAM males. Despite these changes to alcohol intake and CeA GABA signaling, stressed rats showed broadly similar anxiogenic-like behaviors to our previous comorbid model, suggesting decoupling of the PTSD symptoms from the AUD vulnerability for | 3355 KIRSON et al.

Sexually dimorphic effects of monoacylglycerol lipase inhibitor MJN110 on stress‐related behaviour and drinking in Marchigian Sardinian alcohol‐preferring rats

“…We treated male and female Wistar and msP rats with a single dose of MJN110 and assessed the efficacy of pharmacological MAGL inhibition on modulating the number of aggressive and defensive behaviours in the bottle‐brush test. We have previously used the bottle‐brush test (Cruz et al, 2022; Kimbrough et al, 2017; Kirson et al, 2021; Somkuwar et al, 2017; Spierling et al, 2020; Steinman et al, 2021) to assess withdrawal or PTSD irritability‐like behaviours. As expected, the compound did not have any effect in Wistar controls, but it did exert a significant effect in msP rats.…”

Sugars, Alcohol, and Caffeine Intake From Drinks Among Outpatients With Mental Health Disorders in Greece: A Pilot Study

“…These results are consistent with other studies, suggesting a positive association between alcohol consumption and obesity [ 11 ], as well as schizophrenia and affective disorders [ 12 ]. Alcohol dependence and affective disorders are frequently comorbid with varying prevalence and share underlying mechanisms [ 37 ]. Excessive alcohol consumption can worsen the depression course, increase the risk of suicide, and delay recovery from psychiatric conditions [ 30 ].…”

Sex Differences in Addictive Behavior of Adult Rats: Effects of Prenatal Alcohol Exposure

“…Нейрохимические и молекулярные механизмы, лежащие в основе этого феномена, до сих пор мало изучены. Опираясь на данные о значении экстрагипоталамической системы стресса в механизмах острого и хронического действия алкоголя [12,13,16,20] и ключевой роли миндалины мозга в реализации подкрепляющих эффектов этанола и развитии анксиогенеза в остром периоде синдрома отмены алкоголя [15], в настоящем исследовании нами проведена экспериментальная проверка гипотезы о возможной связи аддиктивного поведения пренатально алкоголизированных крыс с нарушением транскрипции кортикотропин-рилизинг фактора (corticotropin-releasing factor, CRF) и его рецептора (CRFR1) в миндалине мозга. Учитывая важность фактора пола в трансляционных исследованиях аддиктивных расстройств [17], нами было проведено сравнительное изучение эффектов пренатальной алкоголизации на потребление алкоголя и экспрессию мРНК CRF и CRFR1 у взрослых самцов и самок крыс.…”