IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2023.12.006

Magda Malewska-Kasprzak , Agnieszka Permoda-Pachuta , Maria Skibińska , Marta Malinowska-Kubiak , Filip Rybakowski , Monika Dmitrzak-Węglarz

Introduction

Consequences of alcohol use disorder (AUD) are associated with mental and somatic burdens that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). So far, biomarkers for tracking abstinence syndrome that are useful in clinical practice have yet to be detected. Current research focuses on brain-derived neurotrophic factor (BDNF) effects on neurogenesis, modulation of plasticity, and its role in the pathogenesis of AWS and DTs.

Aims

The present study aimed to assess pro-BDNF and BDNF concentrations in a group of patients with AWS. Changes in BDNF and prof-BDNF were also evaluated with attention to subgroups of patients with coexisting mental and somatic disorders, with a particular emphasis on the presence or absence of DTs.

Results

The AWS group had a higher concentration of BDNF and a lower concentration of pro-BDNF compared to the control group, and BDNF increased during 7 days of hospitalisation. Patients with comorbid psychiatric disorders had higher levels of pro-BDNF than those without disease and also had higher levels of BDNF at the end of the study than at the beginning. On the other hand, patients with coexisting somatic diseases had higher levels of pro-BDNF at the beginning than at the end of the study, while patients with delirium had higher BDNF levels at the end of the study than at the beginning.

Conclusions

The obtained results indicate that pro-BDNF and BDNF may be useful markers for the course of withdrawal syndrome. In particular, BDNF showed an association with the development of delirium complications. The authors are aware of several limitations of the work only men in the SG, different age between SG and CG.

酒精使用障碍（AUD）的后果与导致酒精戒断综合征（AWS）的精神和身体负担相关，其中30%的AWS病例导致危及生命的震颤谵妄（DTs）。到目前为止，在临床实践中有用的追踪戒断综合征的生物标志物尚未被发现。目前的研究主要集中在脑源性神经营养因子（BDNF）对神经发生的影响、可塑性的调节及其在AWS和DTs发病机制中的作用。目的：本研究旨在评估一组AWS患者中BDNF和BDNF的浓度。BDNF和pro -BDNF的变化也被评估，并关注患有精神和躯体疾病的患者亚组，特别强调是否存在DTs。结果：与对照组相比，AWS组BDNF浓度较高，pro-BDNF浓度较低，且BDNF在住院7天内升高。患有精神疾病的患者比没有疾病的患者有更高水平的BDNF，并且在研究结束时比开始时有更高水平的BDNF。另一方面，患有共存躯体疾病的患者在研究开始时的BDNF水平高于研究结束时，而谵妄患者在研究结束时的BDNF水平高于研究开始时。结论：BDNF pro和BDNF可能是戒断综合征病程的有用标志物。特别是，BDNF显示与谵妄并发症的发展有关。作者意识到这项研究的局限性，即研究对象仅为男性，研究对象与研究对象的年龄不同。

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引用次数: 0

Sex-dependent effects of ethanol withdrawal from a single- and repeated binge episode exposures on social anxiety-like behavior and neuropeptide gene expression in adolescent rats 单次和多次暴饮暴食暴露乙醇戒断对青春期大鼠社交焦虑样行为和神经肽基因表达的性别依赖性影响

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.10.001

Peter T. Penta, Susanna Villarreal, Caitlin I. Rameas, Ella C. Collins, Trevor T. Towner, Elena I. Varlinskaya, David F. Werner

Ethanol withdrawal sensitivity is a risk factor for the development of alcohol use disorder. Heavy episodic drinking during adolescence often encompasses repeated periods of withdrawal. Adolescent intermittent ethanol exposure of laboratory rodents produces several neurobiological deficits that differ between sexes, but the sensitivity to withdrawal as a contributor to the observed sex differences is not clear. The current study assessed the impact of acute withdrawal from a single- and repeated binge ethanol episodes during adolescence as well as protracted abstinence from repeated binge episodes on social anxiety-like behavior (indexed via significant decreases of social investigation) as well as oxytocin (OXT) and vasopressin (AVP) system gene expression in the hypothalamus (HYP) and central amygdala (CeA) in male and female Sprague Dawley rats. Females displayed social anxiety-like behavior during withdrawal from a single binge episode, whereas both sexes showed social anxiety-like changes following acute withdrawal from repeated binge episodes. After a period of protracted abstinence, only males still displayed ethanol-associated social alterations. Analysis of gene expression in separate, non-socially tested subjects revealed that withdrawal from repeated binge episodes during adolescence increased AVP gene expression in the HYP of males and decreased it in females. Males also displayed increased AVP and OXTR gene expression during acute withdrawal from repeated binge episodes in the CeA, with these changes persisting into adulthood. Together, these findings suggest that adolescent females are sensitive to withdrawal from both acute and repeated ethanol exposures, whereas males are sensitive to withdrawal from repeated ethanol exposures, with affective and transcriptional changes persisting into adulthood.

乙醇戒断敏感性是导致酒精使用障碍的一个危险因素。青春期的大量偶发性饮酒往往包括反复的戒断期。实验室啮齿类动物在青春期间歇性接触乙醇会产生多种神经生物学缺陷，这些缺陷在性别上存在差异，但对戒断的敏感性是导致观察到的性别差异的一个因素，这一点尚不清楚。本研究评估了青春期单次和多次暴饮乙醇的急性戒断以及多次暴饮乙醇的长期戒断对雌雄 Sprague Dawley 大鼠社交焦虑样行为（以社交调查的显著减少为指标）以及下丘脑（HYP）和中央杏仁核（CeA）中催产素（OXT）和血管加压素（AVP）系统基因表达的影响。雌性大鼠在单次暴饮暴食后的戒断过程中表现出类似社交焦虑的行为，而雌雄大鼠在多次暴饮暴食后的急性戒断过程中都表现出类似社交焦虑的变化。在长期戒断后，只有雄性大鼠仍表现出与乙醇相关的社交变化。对单独的、非社交测试对象的基因表达分析表明，在青春期因反复酗酒而戒断后，男性 HYP 中的 AVP 基因表达增加，而女性则减少。在CeA中，男性在急性戒断重复酗酒发作时也显示出AVP和OXTR基因表达增加，这些变化一直持续到成年。这些研究结果表明，青春期女性对急性和反复暴露于乙醇的戒断敏感，而男性对反复暴露于乙醇的戒断敏感，其情感和转录变化会持续到成年。

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引用次数: 0

Understanding drunkorexia behaviors among college students using the theory of planned behavior 用计划行为理论理解大学生醉酒行为。

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.12.008

Amir Bhochhibhoya , Shannon N. Speed , Rose Marie Ward , Paul Branscum

Drunkorexia refers to high-risk behaviors that involve the intersection of disordered eating behaviors and risky alcohol consumption. This study utilized the extended Theory of Planned Behavior (TPB) to identify potential psychosocial factors that contribute to drunkorexia among students (484 undergraduate students) from a midwestern Mid-sized university. This cross-sectional study used online surveys designed to measure various drunkorexia-related behaviors including alcohol consumption, calorie restriction, excessive exercise, and purging utilizing antecedents of the TPB. About one-fourth of participants reported engagement in drunkorexia. The extended TPB model reported strong predictive validity for intention for calorie restriction, excessive exercise, and purging with instrumental attitudes and capacity being significant predictors for all three behaviors. Findings provide more profound insight regarding patterns of drunkorexia that could inform future theory-based interventions to address drunkorexia among college students.

暴饮暴食是指饮食紊乱和危险饮酒的高危行为。本研究利用扩展的计划行为理论（TPB）来确定导致美国中西部一所中等规模大学学生（484名本科生）醉酒的潜在社会心理因素。这项横断面研究采用在线调查的方式，旨在测量各种与醉酒有关的行为，包括饮酒、卡路里限制、过度运动和利用TPB前因进行排毒。大约四分之一的参与者报告说自己有过醉酒的经历。扩展的TPB模型报告了对卡路里限制，过度运动和净化的意图的强预测有效性，工具性态度和能力是这三种行为的重要预测因子。研究结果提供了关于醉酒模式的更深刻的见解，可以为未来基于理论的干预措施提供信息，以解决大学生醉酒问题。

引用次数: 0

Burden of alcohol use and inclusion of alcohol use disorder medications in the essential medicine lists across 132 countries: An observational study 132 个国家的酒精使用负担以及将酒精使用障碍药物纳入基本药物清单的情况：一项观察性研究。

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.02.007

Arpit Parmar , Dinesh Prasad Sahu , Priyamadhaba Behera

Harmful use of alcohol affects the health of the population. The treatment coverage of alcohol use disorders (AUD) varies among countries. The study aimed to determine the inclusion of AUD medicines in various national Essential Medicine Lists (EMLs) and its association with alcohol consumption. It was a secondary data analysis of alcohol consumptions and AUD-related medicines in EML. Data were extracted from the WHO Global Essential Medicines database and the WHO Global Status Report on Alcohol and Health 2018. Data were extracted for 194 countries. Only 132 of 194 countries (68.0%) had EML, and among the 132 countries only 27.3% had included AUD medicines in their EML. Only 36 countries had included any of the AUD medicines in their EML. Disulfiram was included by 23 countries, while acamprosate and naltrexone were included by only four and 19 countries, respectively. Among the countries, 36.1% were from upper-middle income countries and 16.65 were from low-income countries. The inclusion of AUD medicines in national EML was neither associated with alcohol consumption parameters nor the alcohol consumption-related policy parameters. Considering the high prevalence of AUD and its complications, there is an urgent need to focus on including AUD medicines in national EMLs for making AUD treatment available and accessible across the world.

有害使用酒精会影响人们的健康。各国对酒精使用障碍（AUD）的治疗覆盖率各不相同。本研究旨在确定各国基本药物清单（EMLs）中包含的 AUD 药物及其与酒精消费的关系。这是一项关于酒精消费和 EML 中 AUD 相关药物的二手数据分析。数据提取自世卫组织全球基本药物数据库和《2018 年世卫组织全球酒精与健康状况报告》。共提取了 194 个国家的数据。在 194 个国家中，只有 132 个国家（68.0%）拥有 EML，而在这 132 个国家中，只有 27.3% 的国家将 AUD 药物纳入其 EML。只有 36 个国家在其 EML 中纳入了任何一种 AUD 药物。有 23 个国家将双硫仑纳入其中，而将阿坎酸和纳曲酮纳入其中的国家分别只有 4 个和 19 个。在这些国家中，36.1%来自中上收入国家，16.65%来自低收入国家。将 AUD 药物纳入国家 EML 既与酒精消费参数无关，也与酒精消费相关政策参数无关。考虑到 AUD 及其并发症的高发病率，迫切需要将 AUD 药物纳入国家 EML，以便在全球范围内提供 AUD 治疗。

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引用次数: 0

Detecting the comorbidity of attention deficit hyperactivity disorder (ADHD) in a population of outpatients with alcohol use disorder (AUD): The role of personality traits, age at first alcohol use and level of craving 检测酒精使用障碍（AUD）门诊患者中注意力缺陷多动障碍（ADHD）的合并症：人格特征、首次饮酒年龄和渴求程度的作用。

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.11.001

Monica L. Roman , Clément Vansteene , Daphnée Poupon , Philip Gorwood

Attention-deficit/hyperactivity disorder (ADHD) commonly affects individuals with alcohol use disorder (AUD). However, despite the negative outcomes associated with this comorbidity, ADHD is underdiagnosed in this population. We aim to identify clinical parameters and propose cutoff scores enabling the detection of ADHD among patients with AUD. We retrospectively analyzed data from 199 patients, out of a global sample of 412 who were consecutively admitted to a day hospital for alcohol-related problems between 2009 and 2022. We found that lower level of self-directedness, higher levels of novelty seeking, self-transcendence, harm avoidance and craving, and earlier first alcohol consumption could accurately predict the presence of ADHD in AUD (AUC = 0.926). Self-directedness and novelty seeking had the best predictive abilities: a self-directedness score below 52 was associated with an accuracy of 82% and, combined with a novelty seeking score over 53, the accuracy reached 85%. Such findings could be useful to help clinicians detect ADHD in patients with AUD so that they can receive the adequate care.

注意力缺陷/多动障碍（ADHD）通常会影响酒精使用障碍（AUD）患者。然而，尽管这种并发症会导致不良后果，但在这一人群中，ADHD 的诊断率却很低。我们旨在确定临床参数，并提出能够在 AUD 患者中发现多动症的临界值。我们回顾性分析了 2009 年至 2022 年间因酒精相关问题连续入住日间医院的 412 名全球样本中的 199 名患者的数据。我们发现，较低的自我导向性、较高的寻求新奇、自我超越、避免伤害和渴求水平以及较早的首次饮酒可准确预测AUD患者是否患有多动症（AUC=0.926）。自我导向性和寻求新奇感的预测能力最强：自我导向性得分低于52分的准确率为82%，加上寻求新奇感得分超过53分，准确率达到85%。这些发现可以帮助临床医生发现AUD患者的多动症，从而为他们提供适当的治疗。

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引用次数: 0

Association between 5-HTRs gene polymorphism and alcohol use disorder in Han males from Yunnan, China 中国云南汉族男性 5-HTRs 基因多态性与酒精使用障碍的关系

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-01-29 DOI: 10.1016/j.alcohol.2025.01.008

Kuan Li , Wei Wei , Yue Wang , Ning Zhang , Jianjun Bao , Xulan Zhang , Xinjian Zheng , Fei Zhao , Xiaopei Yang , Jiahui Peng , Changqing Gao , Shurong Zhong

Alcohol use disorder (AUD) has become a very serious medical and social problem. It is found that genetic polymorphisms of the 5-hydroxytryptamine receptors (5-HTRs) genes were associated with the risk of AUD. However, the results are controversial among different ethnic groups. At present, the correlation between 5-HTRs gene polymorphism and AUD in Han population from Yunnan Province remains unclear. In this study, 13 single nucleotide polymorphisms (SNPs) of HTR1B, HTR2A, HTR3A, HTR3B and HTR7 were detected by universal fluorescent probe technique. The CT genotype frequency of HTR3A rs1062613 was significantly higher in AUD case group than that in control group (P = 0.037, OR = 2.193, 95% CI: 1.048–4.366). The study indicated that the genetic polymorphisms of 5-HTRs were significantly associated with risk of AUD in Han male from Yunnan, China. In addition, this study further demonstrated the impact of alcohol on human health, especially liver damage, by analyzing the blood biochemical indicators of patients with AUD and combining them with their medical history.

酒精使用障碍（AUD）已经成为一个非常严重的医学和社会问题。发现5-羟色胺受体（5-HTRs）基因的遗传多态性与AUD的风险相关。然而，这一结果在不同的种族群体中存在争议。目前，云南汉族人群5-HTRs基因多态性与AUD的相关性尚不清楚。本研究采用通用荧光探针技术检测了HTR1B、HTR2A、HTR3A、HTR3B和HTR7的13个单核苷酸多态性（snp）。AUD病例组HTR3A rs1062613的CT基因型频率显著高于对照组（P = 0.037, OR = 2.193, 95% CI: 1.048 ~ 4.366）。研究表明，5-HTRs基因多态性与中国云南汉族男性患AUD的风险显著相关。此外，本研究通过分析AUD患者的血液生化指标，并结合患者的病史，进一步论证了酒精对人体健康的影响，尤其是对肝脏的损害。

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引用次数: 0

Circulating microRNAs and alcohol consumption in the multiethnic cohort study 多种族队列研究中的循环microrna与酒精消耗

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-01-27 DOI: 10.1016/j.alcohol.2025.01.007

Nicholas Acuna , Song-Yi Park , David V. Conti , Mariana C. Stern , Anna H. Wu , Iona Cheng , Lynne R. Wilkens , Xiao-Ou Shu , Veronica Wendy Setiawan

Excessive alcohol consumption is a significant public health concern and contributes to liver diseases and cancer. Modifiable lifestyle factors including alcohol consumption can influence circulating microRNAs (miRNAs), which are increasingly used as biomarkers for early disease detection. Yet limited studies have identified miRNAs associated with alcohol intake, particularly in multiethnic populations. We aimed to assess the association of alcohol consumption and circulating miRNAs in the Multiethnic Cohort Study. Participants (N = 917) had alcohol consumption data collected at baseline and miRNA data collected at follow-up. Negative binomial models were used to assess the association between alcohol consumption (continuous and categorical [nondrinkers: 0 g of ethanol/day; light drinkers: <28 g of ethanol/day for men and <14 g of ethanol/day for women; and heavy drinkers: ≥28 g of ethanol/day for men and ≥14 g of ethanol/day for women]) and miRNAs. Stratified analyses also examined categories by sex, race/ethnicity, smoking status, and body mass index. Overall, there were 52% non-drinkers, 37 % light drinkers, and 11 % were heavy drinkers. We did not detect an association of miRNAs with alcohol intake in continuous models after correcting for multiple comparisons. However, we did find an inverse association for light drinkers [incidence rate ratio (IRR) = 0.59, p = 8.21E-04] and heavy drinkers (IRR = 0.44, p = 1.47E-03) compared to nondrinkers for miR-451a. Additionally, miR-320e (IRR = 0.63, p = 1.61E-03) had an inverse association with alcohol intake for light drinkers compared to nondrinkers. Subgroup analysis also suggested there were differences by subgroups, underscoring that miRNAs used to detect chronic diseases may be subgroup specific. When stratified by case-control status, we found that among controls both light and heavy drinkers were associated with miR-451a. We identified an association for light and heavy drinkers with miR-451a and mir-320e, miRNAs associated with cancers and liver diseases, in comparison to nondrinkers.

过度饮酒是一个重大的公共卫生问题，会导致肝脏疾病和癌症。包括饮酒在内的可改变的生活方式因素可以影响循环中的microrna (mirna)，而microrna越来越多地被用作早期疾病检测的生物标志物。然而，有限的研究已经确定了与酒精摄入相关的mirna，特别是在多种族人群中。我们的目的是在多种族队列研究中评估饮酒与循环mirna的关系。参与者（N = 917）在基线时收集酒精消耗数据，在随访时收集miRNA数据。使用负二项模型来评估酒精消耗（连续和分类）之间的关系[不饮酒者：0 g乙醇/天；光喝酒:

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引用次数: 0

KCa2 channel positive modulation reduces alcohol drinking in female C57BL/6J mice KCa2通道正向调节减少雌性C57BL/6J小鼠的饮酒。

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-01-27 DOI: 10.1016/j.alcohol.2025.01.005

Kathy L. Lindquist, Audrey E. Padula, Natalie S. Katzenmeyer, Hannah N. Potts, Jennifer A. Rinker, Patrick J. Mulholland

Although men have historically exhibited higher levels of alcohol use disorder (AUD) diagnosis, the gap between men and women has been diminishing quickly. Preclinical screening for pharmacological treatments for AUD has typically focused solely on males, ignoring the possibility that males and females may differ mechanistically for the same behavioral phenotype. To ensure the efficacy of treatment targets across the sexes, it is crucial to study the pharmacological effects of AUD treatments in males and females. While positive K_Ca2 channel modulation can reduce ethanol consumption and seeking behaviors, withdrawal-induced hyperexcitability, and negative affective behaviors in male rodents, the effect of K_Ca2 channel modulation on female ethanol consumption has not been reported. To determine the efficacy of K_Ca2 channel positive modulation in female C57BL/6J mice, we assessed the ability of the K_Ca2 channel positive modulator 1-EBIO to affect locomotor activity, voluntary home cage ethanol intake prior to and following chronic intermittent ethanol (CIE) exposure, and voluntary home cage sucrose drinking. There were no significant changes to distance traveled in an open field apparatus following administration of 1-EBIO in our locomotor assay. In ethanol drinking mice, 1-EBIO significantly reduced ethanol consumption in air controls and CIE exposed mice, without altering water consumption. While administration of 1-EBIO did not affect consumption of sucrose in male mice, 1-EBIO significantly increased sucrose intake in females. Together, these data provide further evidence that K_Ca2 channel positive modulation is a promising therapeutic target to reduce ethanol drinking in males and females alike.

尽管男性在历史上表现出更高的酒精使用障碍（AUD）诊断水平，但男性和女性之间的差距正在迅速缩小。AUD的临床前药物治疗筛查通常只针对男性，而忽略了男性和女性在相同行为表型下可能存在机制差异的可能性。为了确保治疗靶点在性别上的有效性，研究AUD治疗在男性和女性中的药理作用至关重要。虽然正向的KCa2通道调节可以减少雄性啮齿动物的乙醇消耗和寻找行为、戒断诱导的超兴奋性和负面情感行为，但KCa2通道调节对雌性乙醇消耗的影响尚未报道。为了确定雌性C57BL/6J小鼠KCa2通道正向调节的功效，我们评估了KCa2通道正向调节剂1-EBIO对运动活动、慢性间歇性乙醇暴露（CIE）之前和之后自愿在家笼中乙醇摄入以及自愿在家笼中蔗糖饮用的影响。在我们的运动试验中，使用1-EBIO后，在开放场地装置中行走的距离没有明显变化。在饮用乙醇的小鼠中，1-EBIO显著减少了空气对照组和CIE暴露小鼠的乙醇消耗，而不改变水消耗。虽然给药1-EBIO不影响雄性小鼠的蔗糖摄入量，但1-EBIO显著增加了雌性小鼠的蔗糖摄入量。总之，这些数据提供了进一步的证据，证明KCa2通道正调节是一个有希望的治疗靶点，以减少男性和女性的乙醇饮酒。

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引用次数: 0

Effects of daridorexant on rest/wake activity patterns and drinking in adult rats exposed to chronic ethanol vapor in adolescence daridorexant对青春期暴露于慢性乙醇蒸气的成年大鼠休息/清醒活动模式和饮酒的影响。

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-01-25 DOI: 10.1016/j.alcohol.2025.01.006

L.R. Amodeo , D.N. Wills , J. Benedict , C.L. Ehlers

Disturbance in sleep and activity rhythms are significant health risks associated with alcohol use during adolescence. Many investigators support the theory of a reciprocal relationship between disrupted circadian rhythms, sleep patterns, and alcohol usage. However, in human studies it is difficult to disentangle other factors (i.e. lifestyle, psychiatric, genetic) when determining what is causal in the relationship between substance use and sleep/activity disruptions. To this end, we used an animal model of adolescent alcohol exposure whereby male and female Wistar rats are exposed to 5 weeks of intermittent alcohol vapor during adolescence (P22-P57). Five days after ethanol vapor rats were allowed to select to drink alcohol or water in a two-bottle choice procedure for a period of 5 h, 4 days a week for 6 weeks. Activity data was collected using a “Fitbit-like” device during vapor exposure, during acute withdrawal, and after 3 weeks of protracted withdrawal. Significant changes in rest/wake activity and circadian measures were seen during 24-h withdrawal and after 3 weeks of withdrawal. Four weeks following withdrawal, the effects of the dual orexin antagonist, Daridorexant, (DAX 30 mg, 100 mg, or vehicle control), on alcohol drinking and rest and activity rhythms were assessed over a 24 h period. Both daridorexant doses led to changes in circadian measures and rest/wake activity patterns. These results showed that daridorexant reduced activity, but it did not improve rest quality as measured by the mean inactive episode duration and inactive fragmentation ratio. Additionally, we did not find a significant difference in drinking behavior in animals treated with the orexin antagonist. Thus, it appears that data from this animal model do not support the use of this drug to improve adolescent alcohol-induced sleep disturbance and/or to decrease alcohol drinking.

睡眠和活动节奏紊乱与青春期饮酒有关，是重大的健康风险。许多研究者支持昼夜节律紊乱、睡眠模式和饮酒之间存在相互关系的理论。然而，在人类研究中，在确定药物使用与睡眠/活动中断之间的因果关系时，很难理清其他因素（即生活方式、精神病学、遗传）。为此，我们使用了青春期酒精暴露的动物模型，雄性和雌性Wistar大鼠在青春期暴露于5周的间歇性酒精蒸气中（P22-P57）。乙醇雾化后5天，允许大鼠按照两瓶选择程序选择饮酒或喝水，每周4天，持续5小时，持续6周。在蒸汽暴露期间、急性停药期间和持续停药3周后，使用类似fitbit的设备收集活动数据。在24小时停药期间和停药3周后，观察到休息/清醒活动和昼夜节律测量的显著变化。停药4周后，在24小时内评估双食欲素拮抗剂Daridorexant （DAX 30mg、100mg或对照）对饮酒、休息和活动节律的影响。两种高剂量均导致昼夜节律测量和休息/清醒活动模式的变化。这些结果表明，daridorexant降低了活动，但通过平均非活动发作时间和非活动碎片率来衡量，它没有改善休息质量。此外，我们没有发现用食欲素拮抗剂治疗的动物在饮酒行为上有显著差异。因此，这个动物模型的数据似乎不支持使用这种药物来改善青少年酒精引起的睡眠障碍和/或减少饮酒。

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引用次数: 0

Maternal, paternal, and dual-parental alcohol exposures result in both overlapping and distinct impacts on behavior in adolescent offspring 母亲、父亲和双亲酒精暴露对青少年后代的行为既有重叠的影响，又有不同的影响。

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol

Pub Date : 2025-01-22 DOI: 10.1016/j.alcohol.2025.01.004

Kara N. Thomas , Alison Basel , Hayden Reitz , Rachel Toler , Kelly R. Thomas , Luke J. Dotson , Tyler Brown , Alan Nguyen Pham , Siara K. Rouzer , Rajesh C. Miranda , Michael C. Golding

Emerging research reveals that alcohol use by fathers before conception can affect the growth and development of their offspring. Here, we used a C57BL/6J mouse model to study the effects of alcohol exposure on the behavior of the first-generation (F1) offspring, comparing the impacts of alcohol exposure by mothers, fathers, and both parents. Our goal was to determine how alcohol exposure by each parent or both parents influences the behavior of the offspring. We found that adolescent male offspring of alcohol-exposed fathers showed reduced anxiety-like behaviors as they spent more time in the center of the testing arena during the open field test. Both maternal and paternal alcohol exposure caused sex-specific increases in the nestlet shredding test while decreasing the number of buried marbles in the marble burying test. Interestingly, dual-parental alcohol exposure did not produce any significant changes in these same tests. However, during novel object recognition testing, we found that dual-parental male and female offspring exhibit an increased preference for novel objects, suggesting an increased risk preference. Finally, at sixteen weeks, male offspring of dual-exposed parents exhibited decreased voluntary physical activity on running wheels during the active phase, suggesting alterations in their circadian rhythms. Although differences in parental exposure histories between treatment groups make interpretation challenging, our findings suggest that exposure to alcohol by both parents may have unique effects on behavior and that studying both maternal and paternal alcohol use is essential for understanding the full range of factors influencing the penetrance and severity of alcohol-related phenotypes.

最新研究表明，父亲在怀孕前饮酒会影响后代的生长发育。在这里，我们使用C57BL/6J小鼠模型来研究酒精暴露对第一代（F1）后代行为的影响，比较了母亲、父亲和父母双方酒精暴露的影响。我们的目标是确定父母一方或双方的酒精暴露如何影响后代的行为。我们发现，酗酒父亲的青春期男性后代在开放场地测试中，当他们花更多的时间在测试场地的中心时，他们的焦虑行为就会减少。母亲和父亲的酒精暴露均引起雏鸟粉碎试验的性别特异性增加，而大理岩掩埋试验中掩埋大理岩的数量减少。有趣的是，双亲酒精暴露在这些相同的测试中没有产生任何显著的变化。然而，在新物体识别测试中，我们发现双亲双亲的雄性和雌性后代对新物体的偏好增加，这表明风险偏好增加。最后，在16周时，双暴露父母的雄性后代在活动阶段在跑步轮上的自愿体力活动减少，这表明他们的昼夜节律发生了变化。尽管治疗组之间父母接触史的差异使得解释具有挑战性，但我们的研究结果表明，父母双方都接触酒精可能对行为有独特的影响，研究母亲和父亲的酒精使用对于理解影响酒精相关表型外显率和严重程度的所有因素至关重要。

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