American Journal of Drug and Alcohol Abuse最新文献

{"title":"Changes in the proportion of fatal overdoses by substance type in the US, 1999-2021.","authors":"Zachary Sturman, Tami Gurley","doi":"10.1080/00952990.2025.2538545","DOIUrl":"https://doi.org/10.1080/00952990.2025.2538545","url":null,"abstract":"<p><p><i>Background:</i> Recent studies have quantified the rate of fatal overdoses that involve opioids, stimulants, and other drugs, but the proportion of overdose deaths attributable to these substances - after accounting for polysubstance use - has not been determined.<i>Objective:</i> We aim to generate the first estimates of the share of overdose deaths by substance type from 1999 to 2021.<i>Methods:</i> By analyzing the National Vital Statistics System's mortality files, we calculated the percent of overdose deaths (<i>n</i> = 1,043,852, 30% female) by substance type in the US for the years 1999 to 2021. We offer and rely on two novel methods: the single-substance method and the apportioned-substance method.<i>Results:</i> In 2021, opioids accounted for 56% (apportioned-substance) to 64% (single-substance) of overdose deaths and stimulants accounted for 30% (single-substance) to 34% (apportioned-substance), which means that opioids and stimulants accounted for 89% to 94% of overdose deaths. From 1999 to 2021, fentanyl became an increasing share of opioid deaths (from 12%-14% to 78%-87%; <i>p</i> < .01) and methamphetamine became an increasing share of stimulant deaths (from 11%-12% to 60%-70%; <i>p</i> < .01).<i>Conclusion:</i> Opioid deaths and stimulant deaths comprised at least 89% of overdose deaths, and methamphetamine and fentanyl represented rising proportions of fatal overdoses. To prevent drug deaths, resources should be directed primarily to therapies and interventions for opioids and stimulants.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-10"},"PeriodicalIF":2.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with tobacco use, risky alcohol consumption, and concurrent tobacco and risky alcohol use among vocational education students.","authors":"Bolaji Samson Aregbeshola, Christine Paul, Prince Atorkey, Jason Dizon, Lucy Leigh, Flora Tzelepis","doi":"10.1080/00952990.2025.2547714","DOIUrl":"https://doi.org/10.1080/00952990.2025.2547714","url":null,"abstract":"<p><p><i>Background:</i> Understanding which subgroups of vocational education students are more likely to use tobacco and/or alcohol is critical for designing interventions. Previous research has not explored important student subgroups.<i>Objectives:</i> This exploratory study examined tobacco use, risky alcohol consumption not meeting Australian guidelines, and concurrent use by type of vocational training and whether previously unexplored factors were associated with these health behaviors among vocational education students.<i>Methods:</i> A cross-sectional online survey was conducted among 1057 students (66% male) attending 14 Technical and Further Education campuses in New South Wales, Australia.<i>Results:</i> Type of vocational training was not associated with tobacco use, risky alcohol consumption, or concurrent use. Participants who were married/living with a partner (adjusted odds ratio (AOR): 0.69; 95% Confidence Interval (CI) 0.48, 0.99), or unemployed (AOR: 0.60; 95% CI 0.36, 0.99) had significantly lower odds of tobacco use. Indigenous students (AOR: 1.82; 95% CI 1.19, 2.80) or those who experienced symptoms of depression (AOR: 1.69; 95% CI 1.12, 2.55) had significantly higher odds of tobacco use. Participants aged ≥25 years (AOR: 0.59; 95% CI 0.40, 0.88), female (AOR: 0.42; 95% CI 0.29, 0.62), or unemployed (AOR: 0.57; 95% CI 0.37, 0.88) had significantly lower odds of risky alcohol consumption. Unemployed participants (AOR: 0.53; 95% CI 0.30, 0.95) had significantly lower odds of concurrent use. Those who experienced symptoms of anxiety (AOR: 1.55; 95% CI 1.02, 2.37) had significantly higher odds of concurrent use.<i>Conclusion:</i> Vocational education institutes could provide tailored and culturally appropriate interventions targeting students at increased risk of tobacco and/or alcohol use to prevent diseases.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between COVID impact domains and time to buprenorphine treatment disengagement.","authors":"Zoe M Weinstein, Kara M Magane, Sara Lodi, Delilah Doeleman, Alicia S Ventura, Angela R Bazzi, Melissa Davoust, Margaret G Shea, Clara A Chen, Anna Cheng, Jacqueline Theisen, Samantha Blakemore, Richard Saitz","doi":"10.1080/00952990.2025.2544660","DOIUrl":"10.1080/00952990.2025.2544660","url":null,"abstract":"<p><p><i>Background:</i> People with opioid use disorder (OUD) experienced worse outcomes from the COVID-19 pandemic, which disrupted general medical care.<i>Objectives:</i> To quantify COVID-19 impact on OUD treatment disengagement among patients in office-based addiction treatment (OBAT) with buprenorphine.<i>Methods:</i> We recruited 112 outpatients actively on buprenorphine at enrollment from July 2021 to 2022 for telephone surveys within a prospective cohort study. Exposures were six COVID-19 impact domains: personal or family COVID-19 infection, difficulty accessing healthcare/medications, economic stressors, worsening physical or mental health, social isolation, and conflicts and disruptions in the home. The primary outcome was time to OBAT disengagement. We examined associations between each COVID-19 impact domain score and the composite COVID-19 pandemic impact score (a sum of all scores) with time to disengagement using Cox regression models.<i>Results:</i> Average age was 48 years, 56.3% male, 71.2% white/non-Hispanic, 67% Medicaid insurance and 92.9% housed. The majority (74/112) had started in OBAT prior to the pandemic. Median time to disengagement was 271 days. Neither unadjusted nor adjusted analyses showed significant associations between COVID-19 impact domains and time to disengagement. The adjusted hazard ratio for composite COVID-19 impact score was 1.00 (95% CI: 0.99, 1.02).<i>Conclusions:</i> Negative COVID-19 impacts were prevalent among patients in OBAT, but none were significantly associated with time-to-care disengagement. Most patients had multiple protective factors (male, white/non-Hispanic, housed, and Medicaid insurance) and this OBAT rapidly adopted telemedicine, which may have minimized treatment disruption. Preserving patient insurance access and telehealth may maximize OUD treatment retention despite pandemic stressors.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-10"},"PeriodicalIF":2.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding readmission to substance use disorder treatment in Chile: a mixed-method study.","authors":"José Ruiz-Tagle Maturana, Teresita Rocha-Jiménez, Álvaro Castillo-Carniglia","doi":"10.1080/00952990.2025.2544655","DOIUrl":"https://doi.org/10.1080/00952990.2025.2544655","url":null,"abstract":"<p><p><i>Background:</i> Healthcare readmissions are often perceived as negative outcomes. However, in the context of substance use disorder (SUD) treatment, they may reflect both systemic gaps and sustained engagement. Despite their frequency, the determinants of SUD readmission remain underexplored, particularly in Latin America, where non-injected drug use is highly prevalent.<i>Objective:</i> To identify factors associated with SUD treatment readmission and examine contextual influences shaping readmission risk in Chile.<i>Method:</i> We employed a mixed-methods parallel convergent design. Quantitative analyses included 107,559 treatment episodes (84,978 males; 22581 females) recorded from 2010 to 2019. We estimated Average Hazard Ratios (AHR) using a PWP-GT model. Qualitative data from 14 in-depth interviews explored social, familial, and environmental contributors to readmission.<i>Results:</i> Compared to those who did not complete, completing ambulatory treatment was associated with a lower risk of readmission (AHR = 0.83, 95% CI: 0.78-0.88), while no significant effect was found in residential programs. Women had a higher risk of readmission than men in both ambulatory (AHR = 1.36, 95% CI: 1.31-1.42) and residential settings (AHR = 1.42, 95% CI: 1.33-1.51). Qualitative findings revealed reintegration difficulties post-discharge, especially in high-risk environments. Gender roles pressured women to seek treatment, particularly when they were primary caregivers.<i>Conclusion:</i> Support for caregiving responsibilities may enhance treatment retention and reduce readmissions among women. Clinicians and policymakers should consider implementing structured post-discharge follow-up and community-based support systems, especially after residential treatment, to mitigate environmental risks and sustain recovery.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-12"},"PeriodicalIF":2.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketamine to enhance methadone treatment retention in patients with opioid use disorder and co-morbid depression.","authors":"Peter Manza, Annabelle M Belcher, Heather Fitzsimons, Max Spaderna, Aaron D Greenblatt, Hannah C Smith, Meghan Derenoncourt, Donald Gann, Umer Farooq, Mark D Kvarta, Bethany A DiPaula, Sarah Merritt, Ivana Mitic, Carlos A Zarate, Todd D Gould, Eric Weintraub, Sarah M Kattakuzhy","doi":"10.1080/00952990.2025.2541212","DOIUrl":"https://doi.org/10.1080/00952990.2025.2541212","url":null,"abstract":"<p><p><i>Background:</i> Opioid use disorder (OUD) is a chronic relapsing condition with a high mortality rate. While medications such as methadone are valuable first-line therapies, retention is poor, with the highest dropout rates early in a treatment attempt. Poor outcomes are due in part to the very high rates of co-morbid depression in people with OUD, as depression can drive opioid use. Therefore, administering a rapid-acting antidepressant such as ketamine early in a treatment attempt may be an effective strategy to improve outcomes.<i>Objectives:</i> Here, we describe a case series of three patients (two males, one female) diagnosed with OUD initiating methadone treatment and endorsing symptoms of depression, who met criteria for a single-arm open-label feasibility trial (NCT05051449) at an opioid treatment program in Baltimore, Maryland.<i>Methods:</i> Participants underwent a 2-week ketamine regimen (0.5 mg/kg infusion over 40 min, three times per week for 2 weeks).<i>Results:</i> Ketamine was safe and generally well-tolerated. At 10-day follow-up post-ketamine infusions, participant acceptability ratings were mostly favorable. All three patients remained in treatment through the 3-month timepoint with strong treatment adherence. With treatment, self-reported depression symptoms decreased from severe to mild/moderate in two patients, and from moderate to remission in the third.<i>Conclusions:</i> Randomized controlled trials are warranted to test whether ketamine may be a feasible and safe adjunctive treatment for OUD in patients initiating methadone treatment.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol use severity among Hispanic college students: examining social media discrimination, drinking motives, and resilience in a stress and coping framework.","authors":"Miguel Ángel Cano, Raul Caetano, Brian TaeHyuk Keum, Cory L Cobb, Melissa A Lewis, Dana M Litt, Scott T Walters","doi":"10.1080/00952990.2025.2534965","DOIUrl":"https://doi.org/10.1080/00952990.2025.2534965","url":null,"abstract":"<p><p><i>Background:</i> Exposure to <i>racial and ethnic discrimination</i> (RED) is positively associated with alcohol-related outcomes among Hispanics; however, links between RED and alcohol use are poorly understood, particularly when considering RED in social media.<i>Objectives:</i> Study aimed to (1) examine the direct and indirect associations between RED on social media and alcohol use severity (i.e., AUDIT total score) via coping drinking motives (a form of negative reinforcement in which an individual uses alcohol to alleviate/regulate negative emotions) among Hispanic emerging adult college students, and (2) examine if psychological resilience moderates the direct and indirect associations of social media discrimination on alcohol use severity.<i>Methods:</i> A convenience sample of 423 (women = 300, men = 123) Hispanic college students from Texas and Florida completed a cross-sectional online survey. Data were analyzed by conducting a conditional process analysis.<i>Results:</i> Social media discrimination did not have a direct association with alcohol use severity (β = .05, 95% CI=[-.03, .13], <i>p</i> > .05), but it did have a statistically significant indirect association with alcohol use severity via coping drinking motives (β = .08, 95% CI = [.03, .13], <i>p</i> < .05). Further, psychological resilience functioned as a moderator that weakened the indirect association between social media discrimination and alcohol use severity (β = -.14, 95% CI=[-.23, -.05], <i>p</i> < .001).<i>Conclusions:</i> Our conditional process analysis may help guide etiological studies on RED and alcohol use. The data suggest that psychological resilience and coping drinking motives may be relevant constructs for interventions that aim to mitigate the association between RED and alcohol use.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-10"},"PeriodicalIF":2.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of ketamine for the treatment of patients with alcohol use disorder: a systematic review.","authors":"Bhagwat Singh Rathore, Swarndeep Singh, Manushree Gupta, Pankaj Verma","doi":"10.1080/00952990.2025.2535559","DOIUrl":"https://doi.org/10.1080/00952990.2025.2535559","url":null,"abstract":"<p><p><i>Background:</i> Alcohol use disorder (AUD) remains a major global health challenge with limited effective treatments. Ketamine, an NMDA receptor antagonist with rapid anti-craving and neuroplastic effects, has emerged as a promising novel therapy for AUD.<i>Objective:</i> To review the literature examining the safety and efficacy of ketamine for treating AUD.<i>Methods:</i> PubMed and Embase were searched to identify eligible studies published until December 2024. Studies were screened as per the eligibility criteria. Appropriate Joanna Briggs Institute tool was used for risk of bias assessment. A narrative synthesis of findings from the included studies was done. The review protocol was pre-registered in PROSPERO (CRD42022318120).<i>Results:</i> Six studies comprising a total of 605 patients (528 male) from three different countries (USA, UK, Russia) were reviewed. Five of them reported favorable effects of adjunctive ketamine treatment on a range of different alcohol-related outcomes such as abstinence rates or period, alcohol-related craving, and number of heavy drinking days. However, methodological differences including variations in ketamine dosing strategies (route: oral, IV, IM; dose/session: 0.5 mg/kg IV to 2.5 mg/kg IM; number of sessions: 1-3), treatment duration, sample characteristics, and method used for measuring study outcomes led to significant heterogeneity and limited comparability of results. No study reported any serious adverse event or ketamine misuse following ketamine treatment.<i>Conclusion:</i> This review underscored ketamine's potential as an adjunctive treatment for AUD. While promising, considerable variability in dosing, therapeutic approaches, and study designs limits the certainty of evidence. Future research examining the long-term safety and efficacy of ketamine is needed.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-14"},"PeriodicalIF":2.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perceived stigma and its role in substance use disorder treatment completion.","authors":"Kelsey Isman, Salvatore Giorgi, Jennifer D Ellis, Andrew S Huhn, Tingting Liu, Brenda Curtis","doi":"10.1080/00952990.2025.2528778","DOIUrl":"10.1080/00952990.2025.2528778","url":null,"abstract":"<p><p><i>Background:</i> Perceived Substance Use Disorder (SUD) stigma, defined as the awareness of negative societal attitudes toward individuals with SUDs, may discourage treatment-seeking and completion. Unlike self-stigma (negative beliefs about oneself), perceived stigma reflects individuals' perceptions of stigma from the public. While self-stigma has been widely studied, research on perceived stigma's role in shaping treatment outcomes remains limited.<i>Objectives:</i> This study aimed to examine whether higher perceived stigma at treatment intake predicts premature treatment discontinuation and hypothesized that greater perceived stigma would be associated with increased rates of premature treatment discontinuation.<i>Methods:</i> A total of 7,591 participants (70.2% male) from 75 SUD treatment facilities across the United States completed surveys at treatment intake and early in treatment. Perceived stigma was assessed using the Perceived Stigma of Addiction Scale (PSAS). Treatment completion, defined as standard discharge (recommended duration of care), served as the primary outcome. Mixed-effects models evaluated the relationship between perceived stigma and treatment discontinuation while adjusting for demographic, SUD, and mental health-related covariates.<i>Results:</i> Higher perceived stigma significantly predicted an increased likelihood of premature discontinuation (adjusted odds ratio [AOR] = 0.97, 95% CI [0.95, 0.99], <i>p</i> < .001). For each one-unit increase in PSAS score, the odds of treatment completion decreased by 3%. This relationship persisted across all models, even after accounting for covariates.<i>Conclusion:</i> These findings underscore the importance of addressing perceived stigma at treatment intake and its role in predicting treatment retention. Routine screening for stigma and implementing stigma-reduction interventions during care may contribute to better treatment outcomes for individuals with SUDs.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12345134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The protective role of culture and family disapproval on substance use among American Indian adolescents.","authors":"Rachel Girard, Catherine D Trinh, Melissa R Schick, Nichea S Spillane","doi":"10.1080/00952990.2025.2535557","DOIUrl":"https://doi.org/10.1080/00952990.2025.2535557","url":null,"abstract":"<p><p><i>Background:</i> American Indian communities consistently identify adolescent substance use as a major concern. However, limited empirical work has examined how culturally specific protective factors - such as family disapproval and cultural affiliation - interact to influence substance use behavior. Given the importance of kinship networks and cultural continuity, understanding these dynamics is critical for informing culturally grounded prevention strategies.<i>Objectives:</i> This study examines the moderating role of cultural affiliation in the association between family disapproval of substance use and actual use among American Indian adolescents, a population often excluded from national health datasets.<i>Methods:</i> Secondary analysis was conducted using self-report data from the <i>Our Youth, Our Future</i> study, a nationally representative sample of American Indian adolescents attending schools on or near reservations (<i>N</i> = 8,950; 51% female; Mage = 14.64 years, SD = 1.77).<i>Results:</i> Multilevel analyses revealed that family disapproval was negatively associated with lifetime alcohol (b = -0.15, <i>p</i> < .001) and cannabis use (b = -0.34, <i>p</i> < .001), controlling for age. Among adolescents who endorsed use, cultural affiliation moderated the relationship between family disapproval and past-year alcohol and cannabis use. Specifically, family disapproval was significantly associated with lower alcohol use at high (b = -0.01, <i>p</i> = .002) but not low (b = -0.07, <i>p</i> = .48) levels of cultural affiliation. For cannabis use, the association was stronger at high (b = -0.51, <i>p</i> < .001) versus low (b = -0.32, <i>p</i> = .005) levels.<i>Conclusions:</i> Cultural affiliation strengthens the protective effects of family disapproval on substance use among American Indian youth. Findings support culturally responsive, family-based prevention efforts that promote cultural identity and intergenerational communication.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-12"},"PeriodicalIF":2.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of acute binge-like ethanol exposure during the third-trimester equivalent on subicular interneurons in mice.","authors":"Katalina M Lopez, Rafael Mancero-Montalvo, Andrea Iturralde-Carrillo, Adeline Feng, Tori Shaver, Hyemin Choi, Nikita Jaiswal, Javier Kelly-Roman, Pooja A Bhakta, G Jill Chavez, C Fernando Valenzuela","doi":"10.1080/00952990.2025.2529503","DOIUrl":"10.1080/00952990.2025.2529503","url":null,"abstract":"<p><p><i>Background:</i> In animal models, third-trimester-equivalent acute alcohol exposure (TTAAE) leads to cell death in the subiculum, a hippocampal region critical for long-term memory. Proximal and distal regions of the dorsal subiculum have projections that contribute to different aspects of cognitive processing. GABAergic interneurons regulate excitatory pyramidal neurons in the subiculum, but the long-term effects of TTAAE on these interneurons remain unclear.<i>Objective:</i> To test the hypothesis that TTAAE triggers apoptotic pathways in dorsal subiculum interneurons, leading to a persistent reduction in their numbers and alterations in their functional properties during adolescence.<i>Methods:</i> Postnatal day (P) 7 vesicular GABA transporter (VGAT)-Venus mice were injected (2 × 2.5 mg/kg; subcutaneously, 2 hr apart). Cleaved caspase-3 expression was quantified 8 hr after the last injection. Adolescent neuronal and interneuronal densities were quantified using an anti-NeuN marker and Venus fluorescence. Whole-cell patch-clamp recordings were performed from interneurons and pyramidal neurons.<i>Results:</i> TTAAE activated apoptotic pathways in dorsal subicular interneurons in both regions (proximal, <i>p</i> = .005, g = -1.1; distal, <i>p</i> = .003, g = -1.1). Adolescent neuronal density was significantly decreased in exposed males' distal dorsal subiculum (<i>p</i> < .0001, g = -0.8). Ethanol exposure decreased instantaneous frequency evoked by 250-400 pA current injection in fast-spiking GABAergic interneurons only in female mice (250: <i>p</i> = .019, g = -1.08; 300-450: <i>p</i> = .038, g = -1.06 to- 1.18) but did not significantly affect spontaneous inhibitory postsynaptic currents (sIPSCs) evoked by interneuronal GABA release onto pyramidal neurons.<i>Conclusion:</i> TTAAE activates apoptotic pathways in subicular interneurons, leading to long-term, sex-specific changes, reducing male neuron density and altering female interneuron function. These effects may underlie memory deficits demonstrated in mice with TTAAE.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-13"},"PeriodicalIF":2.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}