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

{"title":"Alterations in glucose and insulin resistance following stress and alcohol cues predict alcohol craving in those with AUD and obesity: A preliminary study.","authors":"Zachary M Harvanek, Verica Milivojevic, Rachel Hart, Rajita Sinha","doi":"10.1111/acer.70283","DOIUrl":"https://doi.org/10.1111/acer.70283","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorders (AUD) and obesity (OB) are highly prevalent and often comorbid. Recent evidence suggests potential mechanistic overlap that may impact treatments such as Glucagon-like Peptide 1 receptor agonists (GLP1-RAs) for AUD. While alcohol intake can affect blood glucose control, and chronic alcohol use increases diabetes risk, the interplay between obesity, metabolic function, and provoked alcohol craving in AUD has not been previously assessed. Thus, we asked whether AUD and AUD + OB showed distinct patterns of fasting glucose, insulin, and insulin resistance (HOMA) relative to healthy controls and whether these patterns affect provoked alcohol cravings.</p><p><strong>Methods: </strong>We performed a secondary data analysis of a prior trial of thirty-one 1-month abstinent, inpatient treatment-engaged individuals with AUD (AUD + OB = 7/31) and 41 nonpsychiatric healthy controls (HC + OB = 8/41) who completed 3-day inpatient fasting morning laboratory sessions where they were exposed to stress, alcohol, or neutral-relaxing cues. Repeated assessments of alcohol craving and blood samples to assess insulin and glucose were collected at each laboratory session. Linear mixed models (LMEs) tested interactions between group (AUD vs. HC), lab condition, time points and obesity.</p><p><strong>Results: </strong>The AUD group showed higher glucose levels relative to HC (p = 0.0054). Across laboratory sessions, there were Group (AUD/HC) by Obesity (OB vs. non-OB) interactions for insulin (p = 0.0013) and HOMA (p = 0.0052), where AUD + OB had lower HOMA and insulin levels than HC + OB, but no differences in AUD versus HC groups without obesity were observed. Finally, we found that glucose and HOMA were associated with provoked stress- and alcohol cue-related craving only in the AUD + OB group (all ps < 0.004), with greater glucose and HOMA associated with higher provoked cravings.</p><p><strong>Conclusions: </strong>These preliminary, hypothesis-generating results suggest that individuals with AUD and obesity may have metabolic alterations that contribute to greater alcohol craving and risk of relapse, and support further testing of GLP-1 agonists for AUD in those with AUD and obesity.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 5","pages":"e70283"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846760","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":"A Scoping Review of Preclinical Paradigms for Clinically Tested Medications in Alcohol Use Disorder.","authors":"Steven J Nieto, Suzanna Donato, Wave-Ananda Baskerville, Kaitlin R McManus, Marcelo F Lopez, Howard C Becker, Lara A Ray","doi":"10.1111/acer.70287","DOIUrl":"https://doi.org/10.1111/acer.70287","url":null,"abstract":"<p><p>Despite increasing attention to the neurobiology of alcohol use disorder (AUD), development of effective pharmacotherapies remains limited. Many medications with promising preclinical profiles fail to translate into clinical efficacy. This scoping review characterizes preclinical studies evaluating medications for AUD that have also been tested in human laboratory paradigms or clinical trials. We focus on two widely used paradigms: the two-bottle choice (2BC) task, which measures alcohol consumption and preference, and operant reinstatement models, which capture relapse-like behavior. A systematic search and data extraction identified preclinical studies using 2BC and reinstatement paradigms to evaluate medications that progressed to human testing. Study characteristics (species, strain, sex, outcomes, and sample sizes) were recorded and effect sizes (corrected Cohen's d) were summarized across outcome domains. Ninety-two unique studies met criteria: 74 employing the 2BC paradigm and 18 using operant reinstatement models, including 1731 animals. Rats were the most common species and sex bias was pronounced: 77 2BC studies using only males, five only females, and all 18 reinstatement studies used male rats exclusively. For 2BC consumption, the largest effects were observed for medications with limited studies, such as levetiracetam (d = -4.58), while more extensively tested medications showed moderate effects, including prazosin (d = -0.74) and naltrexone (d = -0.63). For 2BC preference, levetiracetam again showed a large effect in a single study (d = -4.29). In reinstatement models, rimonabant showed the largest effect (d = -3.11), while naltrexone (d = -0.70), baclofen (d = -1.05), and varenicline (d = -0.72) had moderate effects. This review highlights substantial heterogeneity in study design and underutilization of reinstatement and female animals. Medications with moderate, replicable preclinical effects, especially those tested across both 2BC and reinstatement models, may hold greater translational promise. These findings offer key opportunities for enhancing the translational alignment of preclinical AUD pharmacotherapy research.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 5","pages":"e70287"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846812","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 and Stress Together Can Lead to Long-Term, Dementia-Like Deleterious Effects in the Brain.","authors":"Thatiane De Oliveira Sergio, Frederic W Hopf","doi":"10.1111/acer.70308","DOIUrl":"https://doi.org/10.1111/acer.70308","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 5","pages":"e70308"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823861","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":"Predictors and Trajectories of Negative and Positive Interpersonal Dynamics in Remission From Alcohol Use Disorder.","authors":"Samuel F Acuff, Samuel N Meisel, Emily A Hennessy, Kyla L Belisario, Molly L Garber, James MacKillop, John F Kelly","doi":"10.1111/acer.70284","DOIUrl":"https://doi.org/10.1111/acer.70284","url":null,"abstract":"<p><strong>Background: </strong>Research has established social networks as a critical determinant of recovery from alcohol use disorder (AUD), yet limited research exists investigating quality of interpersonal dynamics, especially during the transition to remission from AUD. Positive interpersonal dynamics (friendship and emotional support) may reinforce recovery, whereas negative interpersonal dynamics (hostility and rejection) may undermine it. Identifying determinants of interpersonal dynamic trajectories, including remission, may guide the development of personalized interventions.</p><p><strong>Method: </strong>Naturalistic prospective study of individuals with moderate-severe AUD initiating a new recovery attempt (N = 501, M_age = 41.42, 57.5% female) who were assessed at baseline, and 1.5, 3, 6, 9, and 12 months later on measures of recovery capital, negative and positive interpersonal dynamics (NIH toolkit scales), and other measures assessing demographic, clinical, and psychological process variables (e.g., abstinence self-efficacy). Latent growth models examined trajectories and time-invariant predictors of positive and negative interpersonal dynamics.</p><p><strong>Results: </strong>Negative interpersonal dynamics declined at the first follow-up and flattened over the remainder of the year. These results differed by remission status, with the greatest reduction in negative interpersonal dynamics among those who achieved abstinent remission at 12-month follow-up. Positive interpersonal dynamics did not change significantly throughout the study period. In covariate models, baseline recovery capital predicted positive and negative interpersonal dynamic intercepts and slopes, and there were differences in significant predictors across remission groups.</p><p><strong>Conclusions: </strong>Among those achieving AUD remission (abstinent or non-abstinent) at 12 months, early recovery is marked by reductions in negative interpersonal dynamics, in contrast to those who do not achieve remission. Regardless of outcome, little change was observed in positive interpersonal dynamics. The predictive utility of recovery capital highlights a modifiable outcome that could help improve the quality of interpersonal dynamics in recovery, although confirmation of this relationship is warranted.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 5","pages":"e70284"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846818","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":"Ethanol Alters the Neurexin Landscape in Human Neuroblastoma Cells","authors":"Clara C. Lowe,&nbsp;Kip D. Zimmerman,&nbsp;Rita Cervera-Juanes","doi":"10.1111/acer.70289","DOIUrl":"10.1111/acer.70289","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurexins (NRXNs) are presynaptic adhesion molecules essential for synaptic organization and the regulation of excitatory–inhibitory balance. The molecular diversity of NRXNs arises from alternative promoters and splicing, particularly at splice site 4 (SS4), which dictates ligand binding. Dysregulation of NRXNs has been linked to substance use disorders, but it remains unclear how the expression of NRXN isoforms responds to physiologically relevant amounts of ethanol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human IMR-32 neuroblastoma cells were maintained in an undifferentiated (UnDiff) state or differentiated (Diff) with trans-retinoic acid (tRA) to promote an enrichment in parvalbumin (PV) expression. Cells were exposed to physiologically relevant ethanol concentrations (0, 7, or 35 mM) in vapor chambers. Quantitative polymerase chain reaction (qPCR) quantified mRNA levels of major NRXN transcripts (<i>NRXN1</i>, <i>NRXN2</i>, and <i>NRXN3</i>) and SS4 variants (+SS4, −SS4). Immunocytochemistry (ICC) was used to measure protein expression and overlap with neuroligin2 (NLGN2) and PV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Differentiation increased basal expression of several NRXN transcripts, including <i>NRXN2α</i>, <i>NRXN2 +SS4</i>, <i>NRXN3α</i>, <i>NRXN3β</i>, and <i>NRXN3</i> −<i>SS4</i>. In Diff cells, ethanol-induced dose-dependent downregulation of <i>NRXN2α</i>, <i>NRXN3α</i>, <i>NRXN3β</i>, and <i>NRXN3</i> −<i>SS4</i> transcripts, while <i>NRXN1</i> remained stable. In Diff cells, ICC confirmed isoform-specific protein reductions without changes in other markers (Tuj1 and PV). NRXN3β decreased at 7 and 35 mM; and NRXN1 and NRXN2 at 35 mM. Ethanol significantly reduced overall expression of NRXN3β at 7 and 35 mM; and NRXN1 and NRXN2 at 35 mM, along with NRXN3β-NLGN2 spatial overlap and NRXN1, 2, and 3β signal within PV-positive cells, indicating targeted disruption of inhibitory synaptic organization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Physiologically relevant ethanol exposure alters NRXN expression in an isoform-, splice site-, and differentiation-dependent manner, prominently affecting NRXN3 and the SS4 site. These coordinated transcriptional and proteomic changes suggest that ethanol perturbs NRXN3β-NLGN2 interactions and inhibitory synapse stability, revealing a molecular pathway where alcohol may compromise cortical network excitatory–inhibitory balance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679178","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":"Context-Dependent Extinction and Return of Pavlovian Alcohol-Seeking Behavior in Male and Female Rats","authors":"Taylor A. Simmons,&nbsp;Anagha Deshpande,&nbsp;Alicia R. Daley,&nbsp;Alexander J. Etz,&nbsp;Rueben A. Gonzales,&nbsp;Marie H. Monfils,&nbsp;Hongjoo J. Lee","doi":"10.1111/acer.70296","DOIUrl":"10.1111/acer.70296","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Environmental cues can become conditioned stimuli when associated with alcohol consumption, facilitating alcohol-seeking behavior and increasing relapse risk. Extinguishing alcohol-seeking behavior may reduce cue-induced responses; however, conditioned responding often occurs when the cue is presented in a different context than the one where the behavior was extinguished. Although prior research suggests that males generally show stronger context-dependent return of conditioned appetitive and fear responses, it is not known whether this sex difference extends to conditioned responses to alcohol-associated cues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>After a 5-week alcohol induction period, adult male and female Long–Evans rats underwent Pavlovian conditioning in Context A, where a 15% unsweetened alcohol solution was paired with a light cue. Extinction sessions were conducted in a distinct Context B in the absence of alcohol, followed by a test session in Context B (LTM) and then in Context A.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both sexes successfully extinguished alcohol-seeking behavior in Context B but exhibited robust alcohol-seeking behavior when reintroduced to the alcohol-associated context, Context A. No significant sex differences were observed in the magnitude of reemerged conditioned responding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that changes of context induce alcohol-seeking behavior to return similarly in male and female rats, indicating that sex-independent mechanisms may underlie contextual relapse processes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679186","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":"Using Routinely Collected Data From the Network of Alcohol and Other Drugs Agencies Database to Evaluate the Impact of COVID-19 Lockdowns on Trends in Service Delivery in Outpatient Non-Government Alcohol and Other Drug Treatment Services","authors":"Alison K. Beck,&nbsp;Briony Larance,&nbsp;Bradley Wakefield,&nbsp;Laura Robinson,&nbsp;Isabella Ingram,&nbsp;Robert Stirling,&nbsp;Mei L. Lee,&nbsp;Leanne Hides,&nbsp;Gabrielle Campbell,&nbsp;Peter J. Kelly","doi":"10.1111/acer.70298","DOIUrl":"10.1111/acer.70298","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The COVID-19 pandemic disrupted face-to-face alcohol and other drug (AOD) treatment services and prompted greater use of telehealth. This study measured the impact of COVID-19 on outpatient treatment episodes before, during, and after stay-at-home orders were introduced.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This observational study used routinely collected data from community-based non-government AOD services in New South Wales (NSW), Australia across 4 years (209 7-day intervals from January 1, 2019–January 2, 2023). Interrupted time-series analyses with seasonal autoregressive integrated moving average (ARIMA) modeling estimated weekly changes in outpatient treatment episodes associated with stay-at-home (lockdown) orders, including (1) commencements, (2) planned cessations, and (3) unplanned cessations. Episode counts were also examined by gender (male, female), age group (&lt; 25 years, 25–59 years, ≥ 60 years), principal drug of concern (alcohol, amphetamines, cannabinoids, opioids, and other), and location (metropolitan and non-metropolitan).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;There were no significant level or trend changes in the overall number of &lt;i&gt;episode commencements&lt;/i&gt; (ARIMA (2,0,0)(1,0,0), lockdown one: β_level = −814.85, &lt;i&gt;p&lt;/i&gt; = 0.098; β_slope = 11.14, &lt;i&gt;p&lt;/i&gt; = 0.127; lockdown two: β_level = 317.3, &lt;i&gt;p&lt;/i&gt; = 0.427; β_slope = −3.47, &lt;i&gt;p&lt;/i&gt; = 0.237), &lt;i&gt;planned cessations&lt;/i&gt; (ARIMA (1,0,0)(0,0,1), lockdown one: β_level = −142.1, &lt;i&gt;p&lt;/i&gt; = 0.66; β_slope = 1.16, &lt;i&gt;p&lt;/i&gt; = 0.808; lockdown two: β_level = −199.07, &lt;i&gt;p&lt;/i&gt; = 0.432; β_slope = 0.18, &lt;i&gt;p&lt;/i&gt; = 0.932), or &lt;i&gt;unplanned cessations&lt;/i&gt; (ARIMA (1,0,0), lockdown one: β_level = −92.4, &lt;i&gt;p&lt;/i&gt; = 0.717; β_slope = 1.4, &lt;i&gt;p&lt;/i&gt; = 0.711; lockdown two: β_level = −121.19, &lt;i&gt;p&lt;/i&gt; = 0.563; β_slope = 0.53, &lt;i&gt;p&lt;/i&gt; = 0.732) in outpatient non-government AOD services at either lockdown. For subgroups, during lockdown one, commencements per week increased for metropolitan participants (ARIMA (1,0,0) β_level = −725.12, &lt;i&gt;p&lt;/i&gt; = 0.024; β_slope = 10.07, &lt;i&gt;p&lt;/i&gt; = 0.035) and those with amphetamines (ARIMA(3,0,0)(1,0,0) β_level = −338.44, &lt;i&gt;p&lt;/i&gt; = 0.036; β_slope = 4.68, &lt;i&gt;p&lt;/i&gt; = 0.05) as their principal drug of concern.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The introduction of COVID-19 lockdown measures did not appear to adversely impact the number of NSW non-government AOD outpatient treatment episodes delivered nor the likelihood of unplanned dropout. Our findings illustrate the likely role of telehealt","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655455","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 associated with alcohol abstinence in North American Indigenous youth: Age, gender, and cultural identity","authors":"Lindsey Fisher-Fox,&nbsp;Isabella Locklear,&nbsp;Rachel Girard,&nbsp;Melissa A. Cyders,&nbsp;Meghan Crabtree,&nbsp;Nichea S. Spillane","doi":"10.1111/acer.70253","DOIUrl":"10.1111/acer.70253","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>North American Indigenous youth are at increased risk for alcohol use, yet little literature explores why some choose to abstain from alcohol use. This study aimed to: characterize the reasons why Indigenous youth abstain from alcohol; explore how these reasons vary by age, sex, and whether or not the youth reside on or off a reservation; and examine how reasons for abstaining may mediate the relationship between cultural identity and intentions to drink 5 years in the future.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were sourced from the Substance Use Among American Indian Youth: Epidemiology and Etiology, [United States], 2015–2020 study. Data from 2665 Indigenous youth (48.1% female, <i>M</i>_age = 14.2 (SD = 1.7)) who reported no lifetime alcohol use were extracted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Factor analysis of the reasons for abstaining from alcohol resulted in two factors: to avoid negative consequences and due to social reasons. Females (vs. males), younger (vs. older) youth, and youth who lived on a reservation (vs. those who did not) endorsed avoiding consequences and social reasons as more important (<i>p</i>'s &lt; 0.01). A serial mediation analysis found that, while controlling for age, sex, and reservation-dwelling, social, but not negative consequences, reasons significantly mediated the relationship between cultural identity and intention to drink 5 years in the future (indirect effect = −0.020, <i>p</i> = 0.02, 95% CI [−0.039, −0.005]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results extend previous research on the protective role of cultural identity on alcohol use and suggest that developing social reasons to abstain from alcohol may be a modifiable risk factor to encourage alcohol abstinence in Indigenous youth.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640678","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":"Participant Demographic and Baseline Drinking Factors Can Predict Alcohol Use Disorder Pharmacotherapy Clinical Trial Completion and Drinking Outcomes","authors":"Michaela Hoffman,&nbsp;Raymond F. Anton,&nbsp;Arnie Aldridge","doi":"10.1111/acer.70288","DOIUrl":"10.1111/acer.70288","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Partially due to the complexity associated with conducting trials, there have been relatively few regulatory agency-approved medications for the treatment of alcohol use disorder (AUD). Heterogeneity of study samples, such as participant characteristics (including variation in alcohol consumption) as well as drinking efficacy endpoints, may lead to inconsistency in results and a potential increase in Type II errors. The aim of this study is to begin to fill in the knowledge gap of optimal clinical trial design by analyzing potential predictors of outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Five federally funded and publicly available multisite randomized pharmacotherapy clinical trials for the treatment of AUD using similar methodologies to assess drinking outcomes were included. Three FDA-guided drinking efficacy outcomes were calculated for each study independently and combined: abstinence (no drinking days), no heavy drinking days, WHO 2+ risk drinking level (RDL) reduction as well as a measure of study participant completion. These outcomes were analyzed by logistic regression models including a variety of predictors within the full-study sample as well as among only participants treated with placebo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The number of days abstinent prior to randomization was a strong positive predictor of all three predefined drinking outcomes. Further analysis indicated a cutoff of less than three to five abstinent days before randomization might be optimal. For the WHO 2+ RDL endpoint, those within the “high” or “very-high” risk categories were more likely to meet criteria for successful two or more risk level reductions than “medium” risk. Across various demographic variables, only age (older participants) was associated with better outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that some important prestudy drinking characteristics (e.g., less abstinence and older age) as well as being in a higher risk drinking category should be considered for inclusion in future alcohol pharmacotherapy trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647329","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":"Acute Ethanol Significantly Enhances GABAergic Transmission in the Central Lateral Amygdala of Alcohol-Naïve and Alcohol-Dependent Male Rats","authors":"Emaya M. Moss,&nbsp;Enkhzul Batsaikhan,&nbsp;Samantha Amsden,&nbsp;Dean Kirson","doi":"10.1111/acer.70290","DOIUrl":"10.1111/acer.70290","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The central nucleus of the amygdala (CeA), a key component of the extended amygdala, is critical for mediating behavioral and physiological responses to stress and alcohol exposure. While extensive research has characterized alcohol's effects on GABAergic transmission in the medial CeA (CeM), the lateral CeA (CeL) remains underexplored, despite its central role in upstream signaling within the CeA circuit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we examined the effects of acute ethanol (EtOH) on GABAergic transmission in the CeL of alcohol-naïve and alcohol-dependent male and female Wistar rats. Alcohol dependence was induced using a chronic intermittent ethanol vapor exposure protocol. Whole-cell patch-clamp recordings were conducted on CeL neurons to measure spontaneous inhibitory postsynaptic currents (sIPSCs) at baseline and following acute application of 44 mM EtOH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Acute EtOH significantly increased sIPSC frequency in CeL neurons from male rats, regardless of alcohol history, indicating enhanced presynaptic GABA release. In contrast, female rats showed no significant changes in sIPSC frequency or amplitude following acute EtOH application, whether alcohol-naïve or dependent. Several neuronal properties—including membrane resistance, holding current, and rheobase—were significantly altered in alcohol-dependent females. However, overall spiking characteristics and baseline inhibitory transmission did not differ significantly between naïve and dependent groups within each sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings reveal, for the first time, that acute EtOH produces sex-specific effects on GABAergic transmission in the CeL, enhancing inhibitory signaling in males but not females. This pattern mirrors previous observations in the CeM and underscores the importance of including both sexes in alcohol research. Understanding the mechanisms underlying these differences may inform the development of sex-specific treatments for alcohol use disorder.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"50 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635308","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}