Alcohol (Hanover, York County, Pa.)最新文献

{"title":"Ethanol-induced Nrf2 suppression in the lung is mediated by AP-1-driven expression of miR-144","authors":"Viranuj Sueblinvong,&nbsp;Xian Fan,&nbsp;Justin Guo,&nbsp;Hui Tao,&nbsp;David M. Guidot","doi":"10.1111/acer.70088","DOIUrl":"10.1111/acer.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol use disorders (AUD) increase susceptibility to lung diseases. Ethanol suppresses nuclear factor erythroid 2-related factor 2 (Nrf2), impairing pulmonary antioxidant and immune defenses. We showed that HIV-mediated Nrf2 suppression in the lung is driven by miR-144. We hypothesized that ethanol similarly suppresses Nrf2 by inducing miR-144 in the lung.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>miR-144 expression was quantified in lungs from rats chronically fed an ethanol-containing diet and in rat alveolar epithelial cells (AEC), alveolar macrophages (AMs), and lung fibroblasts (PLF) treated with ethanol. The levels of the AP-1 subunits c-Fos and c-Jun, both total and phosphorylated, were quantified by western immunoblotting in rat PLF. The link between ethanol-induced AP-1 activation and miR-144 expression on Nrf2 and Nrf2-regulated antioxidants was then assessed using c-Fos silencing RNA and AP-1 inhibitors. The impact of manipulating miR-144 expression and/or activity on the expression of Nrf2 and two key Nrf2-dependent antioxidants in ethanol-treated PLF was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>miR-144 expression was increased in the lungs of chronic ethanol-fed rats, and ethanol exposure increased miR-144 expression in AEC and PLF, with a trend toward increased expression in AM. Ethanol induced both total and phosphorylated c-Fos protein and total c-Jun protein in PLF. Inhibiting AP-1 with c-Fos silencing RNA or AP-1 inhibitors blocked ethanol-induced miR-144 expression in PLF. Furthermore, RNA silencing of c-Fos or inhibiting miR-144 restored the expression of Nrf2 and the Nrf2-dependent antioxidants GCLC and NQO-1 in ethanol-treated PLF. In contrast, direct overexpression of miR-144 suppressed Nrf2, GCLC, and NQO-1, thereby reproducing the pathophysiological effects of ethanol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Ethanol induces miR-144 expression in the lung, mediated by AP-1 activation. These steps can be implicated in the ethanol-mediated inhibition of Nrf2 and the downstream suppression of Nrf2-dependent antioxidant and immune defenses. These results suggest that miR-144 could be a novel therapeutic target to mitigate susceptibility to acute inflammatory lung diseases in individuals with AUD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 7","pages":"1424-1434"},"PeriodicalIF":3.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the predictive validity of alcohol-seeking following punishment-imposed abstinence in mice","authors":"Linh Tran,&nbsp;Maria Kuznetsova,&nbsp;Elizabeth E. Manning,&nbsp;Erin J. Campbell","doi":"10.1111/acer.70057","DOIUrl":"10.1111/acer.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A defining feature of alcohol use disorder that has captured the attention of fundamental researchers is “persistent use despite negative consequences.” The last two decades have seen the preclinical field adopt the use of punishment to model the adverse consequences associated with alcohol use. However, existing research has focused on rats as the model of choice and alcohol consumption as the prevailing outcome measure. Additionally, the predictive validity of these models, that is, testing currently approved FDA treatments, is yet to be realized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we examined punishment-imposed abstinence in mice using foot shock and measured reinstatement of alcohol-seeking following exposure to alcohol-associated cues and environmental contexts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We showed that mice voluntarily abstain from alcohol use when it is paired with a foot shock. Alcohol-associated cues and environmental contexts produced reinstatement of alcohol-seeking behavior. Finally, the predictive validity of our model was tested using naltrexone and varenicline, two medications to treat alcohol use disorder. Both naltrexone and varenicline reduced reinstatement of alcohol-seeking in male and female mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Together, these data suggest that mice can display reinstatement of alcohol-seeking behavior following voluntary abstinence, and this model could be used to identify new medications for relapse prevention induced by environmental cues and contexts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 6","pages":"1337-1350"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Docosahexaenoic acid protects against alcohol-induced constriction of cerebral arteries and inhibition of vascular smooth muscle BK channels","authors":"Shiwani Thapa,&nbsp;Rika Morales,&nbsp;Steven Mysiewicz,&nbsp;Sydney Hawks,&nbsp;Elizabeth Tolley,&nbsp;Alex M. Dopico,&nbsp;Anna N. Bukiya","doi":"10.1111/acer.70073","DOIUrl":"10.1111/acer.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid used as a dietary supplement with health benefits. Alcohol in moderate-to-high concentrations constricts cerebral arteries and triggers brain ischemia. Here, we probed the ability of DHA to protect against alcohol action on cerebral artery diameter and on the activity of calcium-/voltage-gated potassium channels of large conductance (BKs) in vasculature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Adult Sprague–Dawley rats received daily oral DHA supplementation for up to 18–23 weeks. Constriction of middle cerebral artery (MCA) pial branches was probed using a cranial window upon infusion of 50 mM alcohol into the cerebral circulation. DHA and alcohol were also probed ex vivo in MCAs upon vessel pressurization at 60 mmHg. DHA's effect on alcohol-induced inhibition of BK channels in MCA myocytes was probed using patch-clamp recording of BK currents at physiological membrane voltage and intracellular calcium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DHA protected males but not females against alcohol-induced vasoconstriction in vivo. Oral DHA increased DHA levels in the MCA of male but not female rats. Arteries from male rats on control chow that were pressurized ex vivo and perfused with 3 μM DHA lost their constriction by alcohol. Incubation of freshly isolated myocytes of male MCAs in DHA prevented alcohol-induced inhibition of BK channels. However, DHA protection was absent when DHA was perfused to excised patches. DHA did not alter the amount of BK channel subunits within the myocyte plasmalemma of male MCAs. DHA protection against alcohol-induced constriction persisted in arteries expressing BK channel with a mutation on a previously identified fatty acid-sensing site.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DHA protects against alcohol-induced cerebral artery constriction and BK channel inhibition in a sexually dimorphic manner via cellular mechanisms in vascular myocytes. This action of DHA is independent of changes in BK subunit membrane levels and of a previously identified fatty acid-sensing site in the BK channel.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 7","pages":"1396-1411"},"PeriodicalIF":3.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144672","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":"Predictors of concerned others' Al-Anon attendance and involvement following adults' entry into treatment for an alcohol use disorder","authors":"Michael A. Cucciare,&nbsp;Xiaotong Han,&nbsp;Kristina Kennedy,&nbsp;Christine Timko","doi":"10.1111/acer.70085","DOIUrl":"10.1111/acer.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol use disorders (AUDs) negatively impact the health of persons consuming alcohol and their concerned others (COs, their family, and friends). It is important to identify factors that affect COs' likelihood of participating in supportive services, such as Al-Anon, that can improve their outcomes. We used the Stress-Strain-Coping-Support model to identify potential predictors of Al-Anon attendance and involvement among COs of adults entering treatment for an AUD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants were 279 dyads of patients entering residential treatment for AUD and their CO. Outcomes were COs' Al-Anon attendance and participation. The study examined patient and CO characteristics at baseline as predictors of COs' Al-Anon attendance and involvement at baseline and 3-, 6-, and 12-month follow-ups, after controlling for COs' demographics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>COs who were of older age, White, and religious were more likely to attend and be involved in Al-Anon, and COs who were currently living with the patient were more likely to be involved in Al-Anon. Patients with more Alcoholics Anonymous involvement and criminal justice engagement had COs who were more likely to attend and/or be involved in Al-Anon. Further, COs who used more nurturing communication were more likely to attend Al-Anon, and COs who were abstinent from alcohol and with poorer mental health were more likely to attend and be involved in Al-Anon.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Understanding factors affecting COs' use of Al-Anon may inform treatment programs and provider efforts to improve the use of these effective and widely available services among COs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 7","pages":"1587-1600"},"PeriodicalIF":3.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144675","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":"Increased alcohol-biased choice behavior in mouse models of high alcohol drinking","authors":"Marcelo F. Lopez,&nbsp;Howard C. Becker","doi":"10.1111/acer.70076","DOIUrl":"10.1111/acer.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rodent models have explored the transition from controlled goal-directed consumption to habitual/compulsive intake using different procedures. This study evaluates the effect of concurrent presentation of sucrose on alcohol intake using two models that induce high levels of alcohol intake in mice that experienced chronic intermittent ethanol (CIE) exposure and/or stress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In Experiment 1, male mice were exposed to four cycles of CIE or control (air) exposure, and once an increase in voluntary alcohol was observed in CIE mice, mice were offered a choice between alcohol or increasing concentrations of sucrose (from 0.75% to 12%; w/v). In Experiment 2, male mice experienced three cycles of CIE exposure, CIE and forced swim stress, control (air) exposure, or forced swim stress. Once elevated voluntary alcohol intake was observed in mice that experienced both CIE and stress, mice were presented with a choice between alcohol and sucrose (from 1.5% to 6%, w/v increased over consecutive days).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mice that experienced CIE exposure (Experiment 1) or CIE exposure and stress (Experiment 2) showed increased alcohol intake. In Experiment 1, the presentation of sucrose at 3% and 12% reduced alcohol intake in control mice. Only the two highest concentrations of sucrose (6% and 12%) affected alcohol intake in CIE-exposed mice. In Experiment 2, concurrent presentation of a 6% sucrose solution decreased alcohol intake in mice that experienced CIE, stress, or control exposure; however, the presentation of sucrose did not influence alcohol intake in mice that experienced both CIE and stress. The amount of sucrose consumed did not differ between groups in both experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These experiments showed that mice that had experienced repeated CIE exposure alone or in combination with stress were more prone to continue their high levels of alcohol intake despite the presence of a sucrose solution as an alternative.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 7","pages":"1435-1444"},"PeriodicalIF":3.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Articles of Public Interest","authors":"","doi":"10.1111/acer.70084","DOIUrl":"https://doi.org/10.1111/acer.70084","url":null,"abstract":"&lt;p&gt;Researchers have identified anxiety and depression symptom trajectories that may help explain the high relapse rates for people who quit drinking. A study published in &lt;i&gt;Alcohol: Clinical and Experimental Research&lt;/i&gt; found that almost a third of people in treatment for alcohol use disorder had symptoms of anxiety or depression, which improved more slowly than is typical–or didn’t improve at all. The study suggests that identifying these symptom trajectories early in treatment may provide important clues as to who may benefit from intensive interventions to reduce the risk of relapse.&lt;/p&gt;&lt;p&gt;More than half of people treated for alcohol use disorder start drinking again within a year. Chronic drinkers often experience symptoms of anxiety and depression when they stop drinking–symptoms that may lead them to start drinking again. Prior studies have found that when people start treatment for alcohol use disorder, they generally have high depression and anxiety symptoms, but those symptoms dissipate within the first few weeks after stopping drinking.&lt;/p&gt;&lt;p&gt;Researchers for this study, however, found that 30 percent of participants did not fit this trajectory–their symptoms either dissipated more slowly or remained high throughout treatment. The large-scale study analyzed electronic medical records of one thousand people who received treatment for alcohol use disorder at a large alcohol treatment program to understand any individual characteristics associated with different trajectories of anxiety and depression during treatment that might explain the high relapse rates. Participants, who had an average age of 43, were assessed for anxiety and depression symptoms during the first week of treatment and then approximately weekly thereafter.&lt;/p&gt;&lt;p&gt;The analysis identified three distinct trajectories of anxiety and depression among participants. A low trajectory group began with lower scores of depression and anxiety, which rapidly declined. A high trajectory group started treatment with higher scores, which declined more slowly over time, and a sustained trajectory group had high scores at intake and minimal reduction in symptoms throughout treatment. While about 70 percent of participants were in the low trajectory groups, about a quarter were in the high trajectory groups, and about five percent were in the sustained trajectory group.&lt;/p&gt;&lt;p&gt;People in this sustained trajectory group may be particularly good candidates for more intensive treatment approaches, such as anti-anxiety medication and anxiety-focused psychotherapy. This group was also more likely to have more severe symptoms of post-traumatic stress disorder at intake, an anxiety disorder, or a depressive disorder. However, symptoms of depression and anxiety at intake, not just diagnoses, more reliably predicted symptom trajectory.&lt;/p&gt;&lt;p&gt;Findings also indicated that women may be at higher risk of relapse than men. Women were more likely to be in the high trajectory compared to the low trajector","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlational and causal modeling of alcohol-related symptoms and internalizing disorder status: Further elucidation of a harm paradox","authors":"Justin Anker,&nbsp;Bryan Andrews,&nbsp;Erich Kummerfeld,&nbsp;Paul Thuras,&nbsp;Matt G. Kushner","doi":"10.1111/acer.70075","DOIUrl":"10.1111/acer.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Individuals with internalizing (anxiety and depressive) disorder (INTD) suffer from an alcohol-related “harm paradox”; that is, they experience more alcohol-related symptoms in aggregate than do others who drink at the same level. Here, we extend this earlier finding by examining the association of INTD with a wide range of individual alcohol-related symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study sample included respondents in the NESARC Wave 3 who reported having consumed alcohol in the past year (<i>N</i> = 24,485). We used logistic regression analysis to identify the association between INTD and risk for 37 individual alcohol symptoms. We used the BOSS causal discovery algorithm to identify the best-fitting causal model for the full dataset and for 100 resampled datasets, each composed of a randomly selected 50% of the full dataset. Causal edges that appeared in at least 80% of the resampled datasets were deemed “highly stable.”</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After controlling for the level of daily alcohol volume and demographic variables, INTD significantly increased the relative odds of having all 37 alcohol-related symptoms measured (ORs ranged from 1.5 to 4.6). Interactions between INTD and the level of alcohol use were largely nonsignificant. Highly stable direct (unmediated) causal edges emanated primarily from INTD to the symptoms of alcohol withdrawal and dependence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Those with INTD are at greater risk for a wide range of alcohol symptoms than others who drink at the same level, even at relatively low levels of alcohol use. We consider that INTD could exert a direct causal influence specifically on withdrawal and dependence symptoms due to overlapping experiential and/or neurobiological aspects of these alcohol use symptoms and INTD. We conclude that the harm paradox likely contributes to the elevated risk of developing alcohol use disorder comorbidity among those with INTD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 7","pages":"1489-1503"},"PeriodicalIF":3.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors that increase risk for alcohol-induced blackouts in high-intensity drinking young adults","authors":"Jennifer E. Merrill,&nbsp;Holly K. Boyle,&nbsp;Roselyn Peterson,&nbsp;Olivia A. Belitsos,&nbsp;Mary Beth Miller,&nbsp;Kate B. Carey,&nbsp;Kristina M. Jackson,&nbsp;Nancy P. Barnett","doi":"10.1111/acer.70074","DOIUrl":"10.1111/acer.70074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol-induced blackouts are prospectively associated with negative drinking outcomes. While typically requiring heavy drinking, blackouts are not reported on all heavy drinking events or by all individuals who drink heavily. This study extends previous research by identifying the young adults most likely to experience blackouts assessed prospectively. Hypotheses focused on previously supported (female sex, White race, younger age, family history of alcohol problems, lower subjective response to alcohol, and higher tolerance) and novel predictors (possible traumatic brain injury; TBI) of alcohol-induced blackouts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Young adults (<i>n</i> = 203, 57% female, <i>M</i>_age = 22.07) recruited for high-intensity drinking (8/10+ drinks/occasion for females/males) completed a baseline survey and a 28-day ecological momentary assessment protocol. Hierarchical linear modeling was used to test between-person predictors of fragmentary (temporary) or en bloc (permanent) blackout likelihood during the 28 days, and moderators of the effect of day-level estimated blood alcohol concentration (eBAC) on blackout likelihood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Controlling for event-level and average eBAC, both types of blackouts were more likely among those with higher subjective response to alcohol. Fragmentary blackouts were more likely among younger participants and those with possible prior TBI. Day-level eBAC was more strongly associated with both types of blackouts among non-Hispanic White participants and those with lower mean eBACs. Day-level eBAC was most strongly associated with fragmentary blackouts among those with a first-order family history of alcohol problems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Younger age and greater sensitivity to alcohol may confer risk for blackouts above and beyond intoxication levels. Future work is needed to understand mechanisms that explain why these factors confer risk for blackouts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 7","pages":"1530-1541"},"PeriodicalIF":3.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112835","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":"Altered activity within the social behavior neural network in adolescent rats following prenatal alcohol exposure and/or early-life adversity","authors":"Parker J. Holman,&nbsp;Linda Ellis,&nbsp;Amanda Chao,&nbsp;Cecilia Mitchell,&nbsp;Charlis Raineki,&nbsp;Joanne Weinberg","doi":"10.1111/acer.70082","DOIUrl":"10.1111/acer.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Social behavior relies on the dynamic, complex, and coordinated activity of a highly conserved “social behavior neural network,” which includes the olfactory bulb (OB), piriform cortex (PCX), lateral septum, medial prefrontal cortex (mPFC), amygdala, paraventricular nucleus of the hypothalamus (PVN), and ventral hippocampus. Prenatal alcohol exposure (PAE) is known to disrupt social behavior development, leading to lifelong social functioning impairments. Individuals with PAE are at heightened risk of experiencing early-life adversity (ELA), which independently affects social behavior development; however, little is known about the combined effects of PAE and ELA on social behavior.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We previously demonstrated that PAE and ELA impact social recognition memory throughout adolescence; here, we combine animal models of PAE and ELA to gain insight into both independent and interactive effects of these insults on social behavior network neural activity in both early and late adolescent male and female rats. We measured neural activity (<i>c-fos</i> mRNA expression) across the network following social recognition memory testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings indicate that both PAE and ELA are associated with altered neural activity in regions supporting social recognition memory, notably the OB, PCX, mPFC, amygdala, and PVN. The direction of these effects and specific regions impacted vary by sex and age at assessment. Importantly, different brain areas exhibit distinct sensitivities to each type of insult, with PAE generally resulting in hypoactivity of the amygdala and ELA altering mPFC activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data contribute to a more complete social neurobehavioral profile, accounting for both PAE and ELA, to support earlier diagnoses and interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 7","pages":"1445-1458"},"PeriodicalIF":3.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of alcohol influence on fear conditioning: A computational model","authors":"Adam Lonnberg,&nbsp;Marian L. Logrip,&nbsp;Alexey Kuznetsov","doi":"10.1111/acer.70071","DOIUrl":"10.1111/acer.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A connection between stress-related illnesses and alcohol use disorders is extensively documented. Fear conditioning is a standard procedure used to study stress learning and links it to the activation of amygdala circuitry. However, the connection between the changes in amygdala circuitry and function induced by alcohol and fear conditioning is not well established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We introduce a computational model to test the mechanistic relationship between amygdala functional and circuit adaptations during fear conditioning and the impact of acute vs. repeated alcohol exposure. Using firing rate formalism, the model generates electrophysiological and behavioral responses in fear conditioning protocols via plasticity of amygdala inputs. The influence of alcohol is modeled by accounting for known modulation of connections within amygdala circuits, which consequently affect plasticity. Thus, the model connects the electrophysiological and behavioral experiments. We hypothesize that alterations within amygdala circuitry produced by alcohol cause abnormal plasticity of amygdala inputs such that fear extinction is slower to achieve and less robust.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In accordance with prior experimental results, both acute and prior repeated alcohol decrease the speed and robustness of fear extinction in our simulations. The model predicts that, first, the delay in fear extinction caused by alcohol is mostly induced by greater activation of the basolateral amygdala (BLA) after fear acquisition due to alcohol-induced modulation of synaptic weights. Second, both acute and prior repeated alcohol shift the amygdala network away from the robust extinction regime by inhibiting activity in the central amygdala (CeA). Third, our model predicts that fear memories formed during acute or after chronic alcohol are more connected to the context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The model suggests how circuit changes induced by alcohol may affect fear behaviors and provides a framework for investigating the involvement of multiple neuromodulators in this neuroadaptive process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 6","pages":"1233-1247"},"PeriodicalIF":3.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}