Alcohol最新文献

{"title":"CT-optimal touch modulates alcohol-cue-elicited heart rate variability in alcohol use disorder patients during early abstinence: A randomized controlled study","authors":"Juliana Harkki ,&nbsp;Pauli Tuovinen ,&nbsp;Veikko Jousmäki ,&nbsp;Goncalo Barreto ,&nbsp;Pekka Rapeli ,&nbsp;Jussi Palomäki ,&nbsp;Jonne Annevirta ,&nbsp;Anna–Helena Puisto ,&nbsp;Francis McGlone ,&nbsp;Heikki Nieminen ,&nbsp;Hannu Alho","doi":"10.1016/j.alcohol.2024.11.004","DOIUrl":"10.1016/j.alcohol.2024.11.004","url":null,"abstract":"<div><div>Alcohol Use Disorder (AUD) is a chronic brain disorder associated with a high risk of relapse and a limited treatment efficacy. Relapses may occur even after long periods of abstinence and are often triggered by stress or cue induced alcohol craving. C-tactile afferents (CT) are cutaneous nerve fibers postulated to encode pleasant affective touch and known to modulate physiological stress responses. However, their translational potential has not yet been explored extensively in controlled clinical trials. This randomized controlled study aimed to investigate the potential of CT stimulation in modulating relapse predicting biomarkers, physiological cue-reactivity, and subjective alcohol craving in AUD patients in early abstinence.</div><div>Twenty-one participants meeting DSM-5 criteria for mild to moderate AUD received CT-optimal touch or a non-CT-optimal control treatment while exposed to neutral, stress-inducing, and alcohol-related visual stimuli. The tactile treatment was provided with a robotic device, eliminating the social elements of touch. Heart rate variability (HRV), salivary cortisol, and subjective craving were assessed at the baseline, during and after the treatment and stimuli exposure.</div><div>The results showed that CT-optimal touch significantly reduced alcohol-cue-elicited standard deviation of normal-to-normal intervals (SDNN) HRV compared to the control group, shifting the HRV reactivity to the direction known to indicate lower relapse susceptibility. Cortisol levels showed no significant differences between the groups, and subjective alcohol craving increased after alcohol cue exposure in both groups.</div><div>This study found that CT-optimal touch modulates autonomic cue-reactivity in AUD patients, encouraging further research on the therapeutic potential of affective touch. Future research should explore the long-term effects and real-world clinical relevance of CT-optimal touch in alcohol relapse prevention.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 19-26"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analgesic effect of oxytocin in alcohol-dependent male and female rats","authors":"John Marendes (Jr.),&nbsp;Marissa A. Muench,&nbsp;Camille L. Young,&nbsp;Amira A. Ghaly,&nbsp;Brendan J. Tunstall","doi":"10.1016/j.alcohol.2024.12.002","DOIUrl":"10.1016/j.alcohol.2024.12.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic alcohol exposure in humans and rodents causes tolerance to the analgesic effects of alcohol, and enhances pain sensitivity during alcohol withdrawal (i.e., hyperalgesia). The available literature suggests a bidirectional enhancement between chronic alcohol consumption and chronic pain sensitivity. We previously found that oxytocin administration could reduce alcohol consumption in alcohol-dependent rats, and now hypothesize that oxytocin, through analgesic action in the central nervous system, could ameliorate the hyperalgesia induced by alcohol-dependence. To test this hypothesis, we assessed the ability of central and peripheral oxytocin administration to alter thermal (Hargreaves assay) and mechanical (Von Frey assay) pain sensitivity, in male and female rats, made alcohol dependent through repeated cycles of chronic-intermittent ethanol-vapor exposure (CIEV; compared to air-exposed controls).</div></div><div><h3>Methods</h3><div>Male and female cohorts of Wistar rats were surgically prepared with an ICV cannula and assigned to two groups matched in terms of initial response in the Hargreaves assay. Rats in the alcohol dependent group were exposed to chronic-intermittent alcohol-vapor, while air-exposed control rats were exposed only to room air and served as the control group. The thermal nociception sensitivity of all rats was monitored via weekly Hargreaves assay to determine alcohol-dependence-induced hyperalgesia in dependent rats. Next, rats were ICV administered oxytocin (0, 0.5, or 5 μg in 2.5 μL saline) prior to Hargreaves testing (Experiment 1) or Von Frey testing (Experiment 2). Finally, rats were IP administered oxytocin (0, 0.1, or 1 mg/kg) prior to Hargreaves testing (Experiment 3) or Von Frey testing (Experiment 4). In a follow-up experiment, female rats were tested to directly compare three methods for applying the Von Frey test.</div></div><div><h3>Results</h3><div>Male and female alcohol-dependent rats developed hyperalgesia, observed in the Hargreaves assay (Experiment 1 &amp; 3), however, hyperalgesia was not so readily observed when the same rats were tested in the Von Frey assay (Experiments 2 &amp; 4, with the exception of female rats in Experiment 4; follow-up testing indicated that the method of Von Frey test employed is likely important to explain this discrepancy). In both the Hargreaves and Von Frey assays, and in both male and female rats, following central or peripheral administration, oxytocin produced analgesia similarly in both alcohol dependent rats and air-exposed controls.</div></div><div><h3>Conclusion</h3><div>Together, these data suggest the oxytocin system could be targeted to produce therapeutic action in disease that produce hyperalgesia such as in alcohol dependence. We discuss methodological considerations and future experiments that could further elucidate a role for oxytocin in the overlapping neurobiology of alcohol dependence and chronic pain.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 27-38"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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 ,&nbsp;Hongjoo J. Lee ,&nbsp;Regina A. Mangieri ,&nbsp;Rueben Gonzales ,&nbsp;Heba Ajmal ,&nbsp;Tanya Hutter","doi":"10.1016/j.alcohol.2024.09.001","DOIUrl":"10.1016/j.alcohol.2024.09.001","url":null,"abstract":"<div><div>The unclear mechanisms of ethanol metabolism in the brain highlight the need for a deeper understanding of its metabolic pathways. This study used <em>in vivo</em> 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 min for 2.5 h, 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. <em>In vivo</em> 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.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 69-76"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related impact of phenobarbital in suppressing prenatal alcohol exposure-related seizures in developing rats","authors":"Tengfei Li ,&nbsp;George Luta ,&nbsp;Prosper N'Gouemo","doi":"10.1016/j.alcohol.2024.12.007","DOIUrl":"10.1016/j.alcohol.2024.12.007","url":null,"abstract":"<div><div>Prenatal alcohol exposure (PAE) during pregnancy can increase the prevalence of <em>N</em>-methyl-<span>d</span>-aspartate (NMDA)-induced generalized tonic-clonic seizures (GTCSs) in developing rats. However, it is unclear whether phenobarbital (PB) can suppress these PAE-related seizures. To explore this knowledge gap, we investigated the effects of acute PB treatment on NMDA-induced seizures in postpartum rats, prenatally exposed to alcohol on gestational day 18 (GD18), at two developmental stages: day 7 (P7), the equivalent of pre-term neonates, and day 15 (P15), the equivalent of full-term neonates. Timed-pregnant female Sprague–Dawley rats were given a single dose of alcohol or its vehicle on GD18 during the second-trimester equivalent. Male and female postpartum rats were tested for the effectiveness of single-dose treatment with either PB or its vehicle in suppressing NMDA-induced seizures. These seizures include wild running-like behavior (WRLB), flexion seizures (FSs), clonic seizures (CSs), generalized tonic-clonic seizures (GTCSs), and tonic seizures (TSs) in P7 and P15 rats. Analyses revealed that P7 rats were more likely to develop GTCSs after PB administration than P15 rats; this effect was associated with shorter latencies to develop NMDA-induced seizures. Moreover, PAE-related seizure severity is less responsive to PB treatment in P7 rats than in P15 rats. These findings suggest that the PAE-related GTCS model in P7 rats can be used to investigate the mechanisms underlying PB-resistant seizures in developing rats.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 39-50"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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 ,&nbsp;Marie A. Doyle ,&nbsp;Megan E. Altemus ,&nbsp;Rishik Bethi ,&nbsp;Sofia H. Lago ,&nbsp;Danny G. Winder ,&nbsp;Erin S. Calipari","doi":"10.1016/j.alcohol.2024.08.004","DOIUrl":"10.1016/j.alcohol.2024.08.004","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 87-99"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol drinking is attenuated by PDE4 inhibition but partial microglia depletion is not sufficient to block stress-induced escalation of alcohol intake in female mice","authors":"Vernon Garcia-Rivas ,&nbsp;Alexa R. Soares ,&nbsp;Merrilee A. Thomas ,&nbsp;Jessica J. Na ,&nbsp;Asia Smith ,&nbsp;Marina R. Picciotto ,&nbsp;Yann S. Mineur","doi":"10.1016/j.alcohol.2024.12.004","DOIUrl":"10.1016/j.alcohol.2024.12.004","url":null,"abstract":"<div><div>Stress is a major contributing factor to binge drinking and development of alcohol use disorders (AUD), particularly in women. Both stress and chronic ethanol can enhance neuroinflammatory processes, which may dysregulate limbic circuits involved in ethanol reinforcement. Clinical and preclinical studies have identified sex differences in alcohol intake in response to neuroinflammatory triggers. Since both cyclic AMP (cAMP) signaling and microglial activation contribute to neuroinflammation, we explored their contribution to stress-induced ethanol drinking in mice. To this end, we first trained C57BL/6J male and female mice to volitionally drink ethanol through a modified version of the “Drinking-in-the-Dark” paradigm. We then assessed whether exposure to foot shock stress followed by repeated exposure to the previously stress-paired context might alter volitional ethanol drinking. We observed that stress exposure resulted in a delayed increase in ethanol intake, but only in female mice. The anti-inflammatory drug Apremilast, an inhibitor of phosphodiesterase type 4 (PDE4; the primary enzyme for cAMP degradation in the brain), reduced ethanol intake and decreased preference for ethanol regardless of stress exposure in females. In contrast, a partial pharmacological depletion of microglia via PLX3397 treatment did not significantly alter baseline ethanol drinking or stress-induced ethanol drinking in female mice. This study shows that female mice are more susceptible to stress-induced ethanol drinking than males, and that this occurs even after partial microglial depletion. In addition, modulation of cAMP signaling by Apremilast administration reduced ethanol drinking regardless of stress exposure, supporting the idea that it might be useful for treatment of AUD.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 31-42"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGF21 responses to alcohol, an insight from a comparative study in individuals with alcohol use disorder","authors":"Suthat Liangpunsakul ,&nbsp;Lorenzo Leggio","doi":"10.1016/j.alcohol.2024.12.001","DOIUrl":"10.1016/j.alcohol.2024.12.001","url":null,"abstract":"","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 11-13"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating microRNA profiling identifies microRNAs linked to prediabetes associated with alcohol dependence syndrome","authors":"Palaniswamy Ramaswamy ,&nbsp;Athira S V ,&nbsp;Pratibha Misra ,&nbsp;V.S. Chauhan ,&nbsp;Arka Adhvaryu ,&nbsp;Anurodh Gupta ,&nbsp;Ankita G ,&nbsp;Sibin M K","doi":"10.1016/j.alcohol.2024.01.003","DOIUrl":"10.1016/j.alcohol.2024.01.003","url":null,"abstract":"<div><h3>Background</h3><div>MicroRNAs are abundant in serum and have emerged as important regulators of gene expression, implicating them in a wide range of diseases. The purpose of this study was to discover and validate serum miRNAs in prediabetes associated with alcohol dependence syndrome (ADS).</div></div><div><h3>Method</h3><div>Serum samples from ADS patients with or without prediabetes and normoglycemic controls were subjected to microarray. Validation of identified candidate miRNAs was performed by RT-qPCR. Additionally, GO and KEGG pathway analyses were carried out to uncover target genes anticipated to be controlled by the candidate miRNAs.</div></div><div><h3>Results</h3><div>Notably, 198, and 172 miRNAs were differentially expressed in ADS-patients with or without prediabetes compared to healthy controls, and 7 miRNAs in ADS-patients with prediabetes compared to ADS-normoglycemic patients, respectively. Furthermore, hsa-miR-320b and hsa-miR-3135b were differentially expressed exclusively in ADS-patients with prediabetes, and this was further validated. Interestingly, GO and KEGG pathway analysis revealed that genes predicted to be modulated by the candidates were considerably enriched in numerous diabetes-related biological processes and pathways.</div></div><div><h3>Conclusion</h3><div>Our findings revealed that ADS-patients with or without prediabetes have different sets of miRNAs compared to normoglycemic healthy subjects. We propose serum hsa-miR-320b and hsa-miR-3135b as potential biomarkers for the diagnosis of prediabetes in ADS-patients.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 101-109"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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 ,&nbsp;C.G. Modrak ,&nbsp;T.D. Thompson ,&nbsp;R.C. Conrad ,&nbsp;I. Leon ,&nbsp;L.A. Knackstedt","doi":"10.1016/j.alcohol.2024.10.002","DOIUrl":"10.1016/j.alcohol.2024.10.002","url":null,"abstract":"<div><div>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 h 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 min 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.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 43-53"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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 ,&nbsp;Pere-Ebi Y. Toloyai ,&nbsp;Adaeze Adebesin ,&nbsp;Vivian O. Ojiokor ,&nbsp;Olusegun G. Adebayo ,&nbsp;Aliance Romain Fokoua ,&nbsp;Goodes E. Moke ,&nbsp;Elo J. Ejukolemu ,&nbsp;Ife-Oluwa O. Akpojevughe ,&nbsp;Abdulkareem M. Abdulkadir ,&nbsp;Ephraim Okwuchi","doi":"10.1016/j.alcohol.2024.07.009","DOIUrl":"10.1016/j.alcohol.2024.07.009","url":null,"abstract":"<div><div>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 (2 g/kg, oral gavage) every other day, alongside daily morin (50 and 100 mg/kg) or fluoxetine (10 mg/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 reduced 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, and stereo-selectively in the mice brains, which morin abated via the preventive mechanisms.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"122 ","pages":"Pages 15-29"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}