Alcohol (Fayetteville, N.Y.)最新文献

{"title":"Single essential oils and their binary mixtures protect against ethanol-induced defects in a zebrafish fetal alcohol spectrum disorder model at the same level as folic acid.","authors":"Andressa Raphaely de Lima Silva, Maria Letícia Santos Carnaúba da Silva, Jadson Freitas da Silva, Katarine Evelyn Falcão E Falcão, James A Marrs, Marilia Ribeiro Sales Cadena, Pabyton Gonçalves Cadena","doi":"10.1016/j.alcohol.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.11.002","url":null,"abstract":"<p><p>This study evaluated protective effects of clove (SEO), thyme white (TEO), oregano (OEO), and caraway (CEO) essential oils (EOs), and their binary mixtures, in a zebrafish fetal alcohol spectrum disorder model. Furthermore, folic acid (FA) was used for comparison as it had previously shown protection against ethanol (EtOH)-induced defects. The co-exposure of zebrafish embryos to EtOH (150 mM) and FA (75 μM) or EOs and their binary mixtures (0.5-1 mg/L) was carried out during 6 or 22 hours postfertilization (hpf). Different developmental endpoints (epiboly measurement, survival rate at 24 hpf, embryonic developmental progression measurement at 24 hpf, larval development at 48-96 hpf, and hatching rate at 72-96 hpf) were evaluated at 8-96 hpf. EtOH exposure reduced epiboly. Only FA and the SEO + TEO binary mixture protected against these defects, and SEO and TEO single exposure showed partial protection. Therefore, these groups were chosen for subsequent experiments. At 24 hpf, EtOH showed developmental delay and hatching rate was delayed at 72 hpf. FA, SEO, TEO, and SEO + TEO partially protected against these defects. This study supports the conclusion that FA partially protects against EtOH-induced defects. SEO and TEO single exposure partially protect against EtOH-induced defects. However, the binary mixture of SEO + TEO was more effective, showing similar efficacy as FA.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of high mobility group box 1 pathway inhibition on gene expression in the prefrontal cortex of mice exposed to alcohol.","authors":"Shuxun Qiu, ShuXin Dong, Jingxin Fan, Wu Chengji, Xunzhong Qi","doi":"10.1016/j.alcohol.2024.10.047","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.10.047","url":null,"abstract":"<p><strong>Introduction: </strong>The high mobility group box 1 (HMGB1) pathway plays a pivotal role in the development of alcohol-induced brain injury. Glycyrrhizinic acid (GlyA) is widely regarded as an inhibitor of HMGB1. The objective is to investigate the impact on gene expression in the prefrontal cortex,we sequenced the transcriptome in control, alcohol-exposed, and HMGB1-inhibited groups of mice. We verified our findings by real-time quantitative PCR (qRT-PCR).</p><p><strong>Methods: </strong>An alcohol exposure model was established in mice by intraperitoneal injection of alcohol. Transcriptome sequencing and bioinformatics analyses were performed on prefrontal cortex tissue. Kyoto Encyclopedia of Genes and Genomes analysis was performed to identify pivotal pathways of differentially expressed genes. The role of relevant genes was verified by qRT-PCR.</p><p><strong>Results: </strong>Expression of genes involved in the neuroactive ligand-receptor interaction pathway exhibited an increase in mice from the alcohol-exposed group.However, there were no significant differences observed in the expression of these genes between control and those receiving an intraperitoneal injection of alcohol along with a HMGB1 inhibitor. Mice in the alcohol-exposed group showed increased gene expression of Cysltr2, Chrna6, Chrna3, Chrnb4, and Pmch. Expression of these genes was decreased in mice injected with HMGB1 inhibitor.</p><p><strong>Significance: </strong>Our study demonstrates that alcohol primarily influences gene expression in the prefrontal cortex of mice through the neuroactive ligand-receptor interaction pathway. HMGB1 inhibitor effectively inhibited the expression of this pathway. This study provides a novel route for drug development in alcohol-induced brain injury.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting the comorbidity of attention deficit hyperactivity disorder (ADHD) in a population of outpatients with alcohol use disorder (AUD): the role of personality traits, age at first alcohol use and level of craving.","authors":"Monica L Roman, Clément Vansteene, Daphnée Poupon, Philip Gorwood","doi":"10.1016/j.alcohol.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.11.001","url":null,"abstract":"<p><p>Attention-deficit/hyperactivity disorder (ADHD) commonly affects individuals with alcohol use disorder (AUD). However, despite the negative outcomes associated with this comorbidity, ADHD is underdiagnosed in this population. We aim to identify clinical parameters and propose cutoff scores enabling the detection of ADHD among patients with AUD. We retrospectively analyzed data from 199 patients, out of a global sample of 412 who were consecutively admitted to a day hospital for alcohol-related problems between 2009 and 2022. We found that lower level of self-directedness, higher levels of novelty seeking, self-transcendence, harm avoidance and craving, and earlier first alcohol consumption could accurately predict the presence of ADHD in AUD (AUC=0.926). Self-directedness and novelty seeking had the best predictive abilities: a self-directedness score below 52 was associated with an accuracy of 82% and, combined with a novelty seeking score over 53, the accuracy reached 85%. Such findings could be useful to help clinicians detect ADHD in patients with AUD so that they can receive the adequate care.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating a 30-day alcohol abstinence challenge in heavy-drinking individuals with and without chronic pain: feasibility, safety, and perceived benefits.","authors":"Dokyoung S You, Maisa S Ziadni, Noel Vest, Nareh Megerdichian, Tara Maronesy, Ralph J Castro, Beth D Darnall, Sean C Mackey, Keith Humphreys","doi":"10.1016/j.alcohol.2024.10.046","DOIUrl":"10.1016/j.alcohol.2024.10.046","url":null,"abstract":"<p><strong>Introduction: </strong>To combat high-risk alcohol consumption, we introduced a 30-day alcohol abstinence challenge targeted at heavy drinkers with and without chronic pain. Our study aimed to assess the challenge's feasibility and safety and to explore its perceived benefits. Our exploratory aim was to identify participants' coping strategies during the challenge.</p><p><strong>Methods: </strong>Our single-arm study recruited heavy drinkers from a pain clinic and a university setting (n = 34, 64.7% chronic pain). Participants underwent a modified community-based 30-day challenge, which included motivational interviewing, an individualized start date, and weekly phone check-ins.</p><p><strong>Results: </strong>We found the 30-day challenge was feasible and safe; 72.3% of eligible heavy drinkers participated in the challenge with no serious adverse events. Most challengers (94.1%) reported some benefit from the challenge, which included improvements in alcohol withdrawal symptoms, sleep, and alcohol abstinence self-efficacy, but not in pain. We identified 25 perceived benefits and 21 coping strategies.</p><p><strong>Conclusion: </strong>Our study confirms that a 30-day alcohol abstinence challenge is a feasible and safe intervention for heavy drinkers with and without chronic pain, yielding notable health benefits. The challenge also facilitated the development of effective coping strategies. Future studies should explore the long-term benefits of such interventions in broader outpatient settings.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consumption of oxycodone prevents oxytocin from attenuating alcohol intake in rats.","authors":"C S Wilkinson, C G Modrak, T D Thompson, R C Conrad, I Leon, L A Knackstedt","doi":"10.1016/j.alcohol.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.10.002","url":null,"abstract":"<p><p>Alcohol and opioid polysubstance use (PSU) is common and often accompanied by higher trait anxiety. Oxytocin decreases anxiety, alcohol- and opioid-seeking and -taking but has not been assessed in the context of PSU. Here we developed a rat model of sequential oxycodone and alcohol PSU to examine the relationship between anxiety, alcohol and oxycodone intake, and the efficacy of systemic oxytocin to attenuate alcohol intake. Male and female Sprague-Dawley rats were assessed for baseline anxiety-like behavior using acoustic startle and the elevated plus maze (EPM). Rats were then given 2-bottle choice access to oxycodone and/or water for 6-hr/day for 7 days, followed by 2-bottle choice access to alcohol (20% v/v) and/or water for five 24-hr sessions across 10 days. Next, monosubstance (oxycodone- or alcohol-alone) rats continued to have access to only one substance/day while PSU rats had access to oxycodone and water for 3-hr, followed by alcohol and water for 6-hr. After 12 days, rats were tested in the EPM 20 hours after alcohol access to examine withdrawal-related anxiety. Next, oxytocin (0, 0.3 or 1.0 mg/kg IP) was administered following the oxycodone/water session, 30 minutes prior to alcohol access. Rats received intragastric oxycodone (2 mg/kg) or water followed by intragastric alcohol (2 g/kg) and blood was collected to determine blood alcohol levels. Elevated baseline anxiety-like behavior was accompanied by reduced alcohol intake. Consumption of oxycodone did not alter alcohol intake but resulted in less anxiety-like behavior during withdrawal and prevented oxytocin from attenuating alcohol intake. Oxytocin (1 mg/kg) reduced alcohol intake in the alcohol-only condition, an effect that persisted for days after a single oxytocin administration. Rats that received oxycodone prior to non-contingent alcohol displayed higher blood alcohol levels than those that did not. These results support the necessity for the testing of medications for substance use in rodent models of PSU.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent effects of ethanol withdrawal from a single- and repeated binge episode exposures on social anxiety-like behavior and neuropeptide gene expression in adolescent rats.","authors":"Peter T Penta, Susanna Villarreal, Caitlin I Rameas, Ella C Collins, Trevor T Towner, Elena I Varlinskaya, David F Werner","doi":"10.1016/j.alcohol.2024.10.001","DOIUrl":"10.1016/j.alcohol.2024.10.001","url":null,"abstract":"<p><p>Ethanol withdrawal sensitivity is a risk factor for the development of alcohol use disorder. Heavy episodic drinking during adolescence often encompasses repeated periods of withdrawal. Adolescent intermittent ethanol exposure of laboratory rodents produces several neurobiological deficits that differ between sexes, but the sensitivity to withdrawal as a contributor to the observed sex differences is not clear. The current study assessed the impact of acute withdrawal from a single- and repeated binge ethanol episodes during adolescence as well as protracted abstinence from repeated binge episodes on social anxiety-like behavior (indexed via significant decreases of social investigation) as well as oxytocin (OXT) and vasopressin (AVP) system gene expression in the hypothalamus (HYP) and central amygdala (CeA) in male and female Sprague Dawley rats. Females displayed social anxiety-like behavior during withdrawal from a single binge episode, whereas both sexes showed social anxiety-like changes following acute withdrawal from repeated binge episodes. After a period of protracted abstinence, only males still displayed ethanol-associated social alterations. Analysis of gene expression in separate, non-socially tested subjects revealed that withdrawal from repeated binge episodes during adolescence increased AVP gene expression in the HYP of males and decreased it in females. Males also displayed increased AVP and OXTR gene expression during acute withdrawal from repeated binge episodes in the CeA, with these changes persisting into adulthood. Together, these findings suggest that adolescent females are sensitive to withdrawal from both acute and repeated ethanol exposures, whereas males are sensitive to withdrawal from repeated ethanol exposures, with affective and transcriptional changes persisting into adulthood.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring epigenetic modification of the stress-related FKBP5 gene in mice exposed to alcohol during early postnatal development.","authors":"Ilknur Dursun, Nur Damla Korkmaz, Sinem Firtina, Muhammed Salih Erkoyuncu, Fahri Akbas, Birsen Elibol","doi":"10.1016/j.alcohol.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.09.002","url":null,"abstract":"<p><p>Early developmental exposure to alcohol has been implicated in adverse effects on the brain, often associated with the onset of neurodevelopmental disorders. Moreover, maternal alcohol consumption during pregnancy has been linked to the manifestation of mental health disorders, such as depression and anxiety, in subsequent generations. These mood disturbances may be attributed to alterations in protein expressions related to depression and anxiety within the hippocampus. While the precise mechanisms remain elusive, it is likely that pre- and postnatal exposure to alcohol induces changes in hippocampus, potentially through epigenetic modifications. The FKBP5 gene, known to modulate the stress response, is particularly relevant in this context. We postulate that alcohol-induced methylation of the FKBP5 gene disrupts HPA axis function, thereby prompting individuals to anxiety-like and depressive-like behaviors. To investigate this hypothesis, female C57BL/6 pups were subjected to early alcohol exposure via intubation with ethanol mixed in artificial milk from Postnatal Day 3 to Day 20. The intubation control pups were subjected to the same procedures without ethanol or milk, and a non-intubated control group included. Anxiety-like and depressive-like behaviors were assessed using the open field test, plus maze test, forced swim test, and tail suspension test when the pups reached 3 months of age. For epigenetic analysis of the FKBP5 gene, genomic DNA was isolated from hippocampal tissues and subjected to bisulfite conversion to distinguish methylated and unmethylated cytosines. Then, methylation-specific PCR was performed to assess methylation levels. Pups exposed to early postnatal alcohol exhibited increased levels of depression-like behavior and susceptibility to anxiety-like behavior during adolescence, as verified by behavioral assessments. Methylation profiling revealed higher rates of methylation within the stress-associated gene FKBP5 in both the early postnatal alcohol-exposed cohort (13.82%) and the intubation control group (3.93%), in contrast to the control cohort devoid of stress or alcohol exposure. These findings suggest a potential epigenetic mechanism underlying the observed behavioral alterations, implicating FKBP5 methylation as a candidate mediator of the increased vulnerability to mood disorders following early postnatal alcohol exposure.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-course concentration of ethanol, acetaldehyde and acetate in rat brain dialysate following alcohol self-administration.","authors":"Tse-Ang Lee, Hongjoo J Lee, Regina A Mangieri, Rueben Gonzales, Heba Ajmal, Tanya Hutter","doi":"10.1016/j.alcohol.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.09.001","url":null,"abstract":"<p><p>The unclear mechanisms of ethanol metabolism in the brain highlight the need for a deeper understanding of its metabolic pathways. This study used in vivo microdialysis to simultaneously sample ethanol and its metabolites, acetaldehyde and acetate, in the rat striatum following self-administration of ethanol, emphasizing the natural oral exposure route. To enhance the self-administration, rats underwent two-bottle-choice and limited access training. Dialysate samples, collected every 10 minutes for 2.5 hours, were analyzed using gas chromatography with flame ionization detection (GC-FID). The measured time courses of dialysate concentrations of ethanol, acetaldehyde, and acetate provided insights into dynamics of ethanol metabolism. Notably, in a subject with low ethanol consumption (0.29 g/kg), the concentration of acetaldehyde remained below the limit of detection throughout the experiment. However, the acetate concentration was clearly increased after ethanol consumption in this subject and was comparable to that of other rats with higher ethanol consumption. Compared with focusing only on peak values in the time-courses of concentrations of ethanol and its metabolites, calculating areas under curves provided better models of the relationships between ethanol intake and individual ethanol metabolites, as indicated by the r-square values for the linear regressions. This approach of using the area under the curve accounts for both the amplitude and duration of the concentration profiles, reducing the impact of variations in individual drinking patterns. In vivo microdialysis enables concurrent sampling of brain metabolites during oral ethanol administration, contributing insights into metabolite dynamics. To our knowledge, this paper is the first to report measurement of all three analytes in the brain following self-administration of ethanol. Future studies will explore regional variations and dynamics post-ethanol dependence, further advancing our understanding of ethanol metabolism in the brain.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Operant ethanol self-administration behaviors do not predict sex differences in continuous access home cage drinking.","authors":"Hye Jean Yoon, Marie A Doyle, Megan E Altemus, Rishik Bethi, Sofia H Lago, Danny G Winder, Erin S Calipari","doi":"10.1016/j.alcohol.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.08.004","url":null,"abstract":"<p><p>Understanding sex differences in disease prevalence is critical to public health, particularly in the context of alcohol use disorder (AUD). The goal of this study was to understand sex differences in ethanol drinking behavior and define the precise conditions under which sex differences emerge. Consistent with prior work, C57BL/6J females drank more than males under continuous access two-bottle choice conditions. However, using ethanol self-administration - where an operant response results in access to an ethanol sipper for a fixed time period - we found no sex differences in operant response rates or ethanol consumption (volume per body weight consumed, as well as lick behavior). This remained true across a wide range of parameters including acquisition, when the ethanol sipper access period was manipulated, and when the concentration of the ethanol available was scaled. The only sex differences observed were in total ethanol consumption, which was explained by differences in body weight between males and females, rather than by sex differences in motivation to drink. Using dimensionality reduction approaches, we found that drinking behavior in the operant context did not cluster by sex, but rather clustered by high and low drinking phenotypes. Interestingly, these high and low drinking phenotypes in the operant context showed no correlation with those same categorizations in the home cage context within the same animals. These data underscore the complexity of sex differences in ethanol consumption, highlighting the important role that drinking conditions/context plays in the expression of these differences.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol-exacerbates post-traumatic stress psychiatric behavior and its neuropathological sequalae in experimental mice: preventive effects of morin.","authors":"Benneth Ben-Azu, Pere-Ebi Y Toloyai, Adaeze Adebesin, Vivian O Ojiokor, Olusegun G Adebayo, Aliance Romain Fokoua, Goodes E Moke, Elo J Ejukolemu, Ife-Oluwa O Akpojevughe, Abdulkareem M Abdulkadir, Ephraim Okwuchi","doi":"10.1016/j.alcohol.2024.07.009","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.07.009","url":null,"abstract":"<p><p>Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are very prevalent and co-occurring. It is unclear how alcohol exacerbates PTSD predicaments owing to less characterized pathophysiological mechanisms. Also, studies on pharmacological agents that can effectively reverse PTSD-AUD comorbidity have, to date, been scarce. Hence, we designed a methodological approach to investigate the pathophysiological mechanisms and pharmacological outcomes of morin, a neuroprotective flavonoid in mice. After 7 days of PTSD following single-prolonged stress (SPS) induction in mice, the PTSD mice were exposed to intermittent binge ethanol administration using ethanol (2g/kg, oral gavage) every other day, alongside daily morin (50 and 100mg/kg) or fluoxetine (10mg/kg) from days 8-21. The consequences of PTSD-AUD behavior, hypothalamic-pituitary-adrenal-axis (HPA-axis) dysfunction, neurochemistry, oxidative/nitrergic stress, and inflammation were evaluated in the prefrontal-cortex (PFC), striatum, and hippocampus of mice. The exacerbated anxiety-like behavior, and spatial/non-spatial memory deficits, with general depressive phenotypes and social stress susceptibility by SPS-ethanol interaction, were alleviated by morin and fluoxetine, evidenced by reduced corticosterone release and adrenal hypertrophy. SPS-ethanol exacerbates dopamine, serotonin, and glutamic acid decarboxylase alterations, and monoamine oxidase-B and acetylcholinesterase hyperactivities in the striatum, PFC, and hippocampus, respectively, which were prevented by morin. Compared to SPS-ethanol aggravation, morin prevented TNF-α, and IL-6 release, malondialdehyde and nitrite levels, with improved antioxidant (glutathione, superoxide-dismutase, catalase) levels in the hippocampus, PFC, and striatum. Overall, these findings suggest that AUD exacerbated PTSD might be primarily connected, among other mechanisms, with aggravated HPA-axis dysfunction, upregulated neurochemical degradative enzymes, enhancement of oxidative/nitrergic stress and neuroinflammation, stereo-selectively in the mice brains, which morin abated via the preventive mechanisms.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}