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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 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 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 KCa2 channel modulation can reduce ethanol consumption and seeking behaviors, withdrawal-induced hyperexcitability, and negative affective behaviors in male rodents, the effect of KCa2 channel modulation on female ethanol consumption has not been reported. To determine the efficacy of KCa2 channel positive modulation in female C57BL/6J mice, we assessed the ability of the KCa2 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 KCa2 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 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 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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引用次数: 0
Sex and gender differences in alcohol use disorder: Quo Vadis? 酒精使用障碍的性别差异:现状?
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-19 DOI: 10.1016/j.alcohol.2025.01.003
Katie Witkiewitz , Lorenzo Leggio
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引用次数: 0
The mediating role of impulsivity on suicidal behaviour among higher education students with depression and substance abuse disorders 冲动性对抑郁症和药物滥用障碍大学生自杀行为的中介作用。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-16 DOI: 10.1016/j.alcohol.2025.01.002
Rachel McHugh , Margaret McLafferty , Natasha Brown , Caoimhe Ward , Colum P. Walsh , Anthony J. Bjourson , Louise McBride , John Brady , Siobhan O'Neill , Elaine K. Murray

Background

Alcohol and drug dependent individuals have consistently exhibited elevated impulsivity and some studies have indicated that impulsivity recorded in young adults predicts future alcohol abuse. Research also indicates that depressed individuals with higher impulsivity are more likely to report suicidal ideation even when they are less depressed, which may indicate that impulsivity could more strongly predict suicidality than severity of depressive symptoms.

Objective

The aim of this study was to investigate the mediating role of impulsivity on suicidal behaviour and self-harm among students with depression, alcohol and substance abuse disorders.

Materials and methods

Participants were first-year undergraduate students (n = 1829) across Ulster University (NI) and Letterkenny Institute of Technology - now known as Atlantic Technological University Donegal (ROI), who were recruited as part of the World Mental Health International College Student Initiative. Participants completed an online survey utilising the WMH-Composite International Diagnostic Interview Screening Scales (CIDI-SC). Mediation analyses were conducted in three different stages.

Results

A high prevalence of depression and substance use disorders, suicidal ideation, plans, attempts and self-harm were observed. Impulsivity was found to partially mediate the association between depression and suicidal behaviours and substance use disorders and suicidal behaviours. Impulsivity was significantly associated with suicide ideation, attempts and self-harm, but not suicide plans. Males were more likely to be impulsive, and higher levels of depression and substance use disorders were related to higher impulsivity.

Conclusions

The main findings of this study reinforce the role of impulsivity in mediating the relationship between depression and suicidality and substance use and suicidality. College wellbeing services may consider whether screening for impulsivity, rather than for example substance abuse, could be more beneficial and less prone to under-reporting, when assessing for suicide risk among vulnerable students.
背景:酒精和药物依赖个体一直表现出较高的冲动性,一些研究表明,记录在年轻人中的冲动性预示着未来的酒精滥用。研究还表明,冲动性较高的抑郁个体即使在抑郁程度较轻的情况下也更有可能报告自杀念头,这可能表明冲动性比抑郁症状的严重程度更能预测自杀行为。目的:探讨冲动性对抑郁、酒精和药物滥用障碍学生自杀和自残行为的中介作用。材料和方法:参与者是阿尔斯特大学(NI)和莱特肯尼理工学院(ROI)的一年级本科生(n=1829),他们是作为世界心理健康国际大学生倡议的一部分招募的。参与者使用wmh复合国际诊断访谈筛选量表(CIDI-SC)完成了一项在线调查。中介分析分三个阶段进行。结果:抑郁症、药物使用障碍、自杀意念、自杀计划、自杀企图和自残的发生率较高。冲动性在抑郁与自杀行为、物质使用障碍与自杀行为之间起部分中介作用。冲动与自杀意念、自杀企图和自残显著相关,但与自杀计划无关。男性更容易冲动,更高程度的抑郁和物质使用障碍与更高的冲动有关。结论:本研究的主要发现强化了冲动性在抑郁与自杀、物质使用与自杀之间的中介作用。在评估弱势学生的自杀风险时,大学福利服务部门可能会考虑是否筛查冲动,而不是药物滥用,可能更有益,更不容易漏报。
{"title":"The mediating role of impulsivity on suicidal behaviour among higher education students with depression and substance abuse disorders","authors":"Rachel McHugh ,&nbsp;Margaret McLafferty ,&nbsp;Natasha Brown ,&nbsp;Caoimhe Ward ,&nbsp;Colum P. Walsh ,&nbsp;Anthony J. Bjourson ,&nbsp;Louise McBride ,&nbsp;John Brady ,&nbsp;Siobhan O'Neill ,&nbsp;Elaine K. Murray","doi":"10.1016/j.alcohol.2025.01.002","DOIUrl":"10.1016/j.alcohol.2025.01.002","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol and drug dependent individuals have consistently exhibited elevated impulsivity and some studies have indicated that impulsivity recorded in young adults predicts future alcohol abuse. Research also indicates that depressed individuals with higher impulsivity are more likely to report suicidal ideation even when they are less depressed, which may indicate that impulsivity could more strongly predict suicidality than severity of depressive symptoms.</div></div><div><h3>Objective</h3><div>The aim of this study was to investigate the mediating role of impulsivity on suicidal behaviour and self-harm among students with depression, alcohol and substance abuse disorders.</div></div><div><h3>Materials and methods</h3><div>Participants were first-year undergraduate students (n = 1829) across Ulster University (NI) and Letterkenny Institute of Technology - now known as Atlantic Technological University Donegal (ROI), who were recruited as part of the World Mental Health International College Student Initiative. Participants completed an online survey utilising the WMH-Composite International Diagnostic Interview Screening Scales (CIDI-SC). Mediation analyses were conducted in three different stages.</div></div><div><h3>Results</h3><div>A high prevalence of depression and substance use disorders, suicidal ideation, plans, attempts and self-harm were observed. Impulsivity was found to partially mediate the association between depression and suicidal behaviours and substance use disorders and suicidal behaviours. Impulsivity was significantly associated with suicide ideation, attempts and self-harm, but not suicide plans. Males were more likely to be impulsive, and higher levels of depression and substance use disorders were related to higher impulsivity.</div></div><div><h3>Conclusions</h3><div>The main findings of this study reinforce the role of impulsivity in mediating the relationship between depression and suicidality and substance use and suicidality. College wellbeing services may consider whether screening for impulsivity, rather than for example substance abuse, could be more beneficial and less prone to under-reporting, when assessing for suicide risk among vulnerable students.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"124 ","pages":"Pages 89-96"},"PeriodicalIF":2.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Indirect effects of perceived stress and depression on the relationship between insomnia symptoms and hazardous drinking 感知压力和抑郁对失眠症状和危险饮酒之间关系的间接影响。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-04 DOI: 10.1016/j.alcohol.2025.01.001
Justin J. Verlinden , Mairead E. Moloney , Olga A. Vsevolozhskaya , Lauren N. Whitehurst , Jessica Weafer
Insomnia is a risk factor for hazardous drinking, yet the mechanisms underlying this risk are not well characterized. Two factors that might contribute to the relationship between insomnia and drinking are stress and depression. Insomnia is strongly associated with increased stress and depression, which are, in turn, strongly linked to hazardous drinking. Here we conducted a preliminary investigation to determine whether perceived stress and depression indirectly explain the relationship between insomnia and hazardous drinking. Heavy drinkers with self-reported insomnia (n = 405: 270 women, 134 men, 1 non-binary) completed self-report measures of hazardous drinking, insomnia, perceived stress, and depression. Results from our primary cross-sectional parallel mediation model with insomnia as the predictor and hazardous drinking as the outcome showed that, when accounting for the influence of both perceived stress and depression, there was a partial indirect effect of insomnia on hazardous drinking through perceived stress, 95% CI [0.014, 0.205], but not depression, 95% CI [-0.080, 0.172]. In our competing cross-sectional parallel mediation model with hazardous drinking as the predictor and insomnia as the outcome, there was a partial indirect effect of hazardous drinking on insomnia through depression 95% CI [0.016, 0.059], but not perceived stress 95% CI: [-0.026, 0.011]. Results suggest that insomnia may be related to hazardous drinking through its effects on stress and that hazardous drinking may be related to insomnia through its effects on depression. These findings lay the groundwork for future longitudinal studies assessing the causal roles of stress and depression in the insomnia-AUD relationship.
失眠是危险饮酒的一个风险因素,但这种风险背后的机制还没有很好地描述。可能导致失眠和饮酒之间关系的两个因素是压力和抑郁。失眠与压力和抑郁的增加密切相关,而压力和抑郁又与酗酒密切相关。在这里,我们进行了一项初步调查,以确定感知压力和抑郁是否间接解释了失眠和危险饮酒之间的关系。重度饮酒者自我报告失眠(n = 405: 270名女性,134名男性,1名非二元)完成了危险饮酒,失眠,感知压力和抑郁的自我报告测量。我们以失眠为预测因子,危险饮酒为结果的主要横断面平行中介模型的结果显示,当考虑到感知压力和抑郁的影响时,失眠通过感知压力对危险饮酒有部分间接影响,95% CI[0.014, 0.205],但95% CI[-0.080, 0.172]不存在。在我们以危险饮酒为预测因子,失眠为结果的竞争性横断面平行中介模型中,危险饮酒通过抑郁(95% CI[0.016, 0.059])对失眠有部分间接影响,但感知压力(95% CI:[-0.026, 0.011])没有影响。结果表明,失眠可能与危险饮酒有关,因为它对压力的影响,而危险饮酒可能与失眠有关,因为它对抑郁的影响。这些发现为未来的纵向研究奠定了基础,以评估压力和抑郁在失眠- aud关系中的因果作用。
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引用次数: 0
Age-related impact of phenobarbital in suppressing prenatal alcohol exposure-related seizures in developing rats 苯巴比妥抑制发育大鼠产前酒精暴露相关癫痫发作的年龄相关性影响
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-26 DOI: 10.1016/j.alcohol.2024.12.007
Tengfei Li , George Luta , Prosper N'Gouemo
Prenatal alcohol exposure (PAE) during pregnancy can increase the prevalence of N-methyl-d-aspartate (NMDA)-induced generalized tonic-clonic seizures (GTCSs) in developing rats. However, it is unclear whether phenobarbital (PB) can suppress these PAE-related seizures. To explore this knowledge gap, we investigated the effects of acute PB treatment on NMDA-induced seizures in postpartum rats, prenatally exposed to alcohol on gestational day 18 (GD18), at two developmental stages: day 7 (P7), the equivalent of pre-term neonates, and day 15 (P15), the equivalent of full-term neonates. Timed-pregnant female Sprague–Dawley rats were given a single dose of alcohol or its vehicle on GD18 during the second-trimester equivalent. Male and female postpartum rats were tested for the effectiveness of single-dose treatment with either PB or its vehicle in suppressing NMDA-induced seizures. These seizures include wild running-like behavior (WRLB), flexion seizures (FSs), clonic seizures (CSs), generalized tonic-clonic seizures (GTCSs), and tonic seizures (TSs) in P7 and P15 rats. Analyses revealed that P7 rats were more likely to develop GTCSs after PB administration than P15 rats; this effect was associated with shorter latencies to develop NMDA-induced seizures. Moreover, PAE-related seizure severity is less responsive to PB treatment in P7 rats than in P15 rats. These findings suggest that the PAE-related GTCS model in P7 rats can be used to investigate the mechanisms underlying PB-resistant seizures in developing rats.
妊娠期产前酒精暴露(PAE)可增加发育大鼠n -甲基- d -天冬氨酸(NMDA)诱导的全身性强直-阵挛性癫痫(GTCSs)的患病率。然而,尚不清楚苯巴比妥(PB)是否能抑制这些与pae相关的癫痫发作。为了探索这一知识差距,我们研究了急性PB治疗对产后大鼠nmda诱导癫痫发作的影响,这些大鼠在妊娠第18天(GD18)暴露于酒精中,在两个发育阶段:第7天(P7),相当于早产儿,第15天(P15),相当于足月新生儿。在妊娠中期等量给予妊娠期雌性Sprague-Dawley大鼠单剂量酒精或其载体GD18。用单剂量PB或其载体对雄性和雌性产后大鼠进行抑制nmda诱导癫痫发作的效果试验。P7和P15大鼠的发作包括狂奔样行为(WRLB)、屈曲性发作(FSs)、阵挛性发作(CSs)、全身性强直-阵挛性发作(GTCSs)和强直性发作(TSs)。分析显示,P7大鼠比P15大鼠更容易在给药后发生gtcs;这种效应与nmda诱发癫痫发作的潜伏期较短有关。此外,P7大鼠与P15大鼠相比,pae相关的gtcs对PB治疗的反应较差。这些发现提示P7大鼠pae相关的GTCS模型可用于研究发育中大鼠pb抵抗性癫痫发作的机制。
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引用次数: 0
Assessing the relationship between mental health and AUDIT score among older sexual and gender minorities 评估老年性少数群体和性别少数群体心理健康与审计评分之间的关系。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-24 DOI: 10.1016/j.alcohol.2024.12.005
Nathaniel Albright , Ethan Morgan

Introduction

Alcohol use, and its relationship with mental health outcomes, remains a public health priority. Yet, little research has focused on this association among aging sexual and gender minority (SGM) populations with even less dedicated to the unique issues of those aging with HIV, a gap we begin to fill here.

Methods

Data for this analysis originated from the Columbus Healthy Aging Project (CHAP), a cross-sectional survey among adults ≥50 years who reside in the Columbus, Ohio. Multivariable linear regression models were utilized to assess the relationship between alcohol use (via AUDIT score) and several mental health outcomes (e.g., depression, anxiety, perceived stress, and sexual orientation microaggressions), adjusting for demographic characteristics and other risk factors. Models were assessed for moderation by self-reported HIV status.

Results

Among the entire sample (N = 787), mean perceived stress score was 18.2 (SD = 5.5), mean anxiety score was 9.1 (5.9), and mean depression score was 9.9 (SD = 6.7). 32 (7.4%) self-reported as PLWH. Among those reporting any alcohol use, mean AUDIT score use was 10.5 (SD = 10.9). Each of the mental health outcome measures were positively associated with AUDIT score. Meanwhile, there was significant moderation of each of the mental health outcome measures by HIV status, suggesting a stronger association with AUDIT score in each case.

Conclusion

Our results suggest that there are broad stressors impacting alcohol use not only among older SGM broadly but in particular among PLWH. Although a diverse set of results, these data highlight the need for more research on alcohol use among aging SGM populations, particularly PLWH and those identifying as a different gender identity.
酒精使用及其与心理健康结果的关系仍然是一个公共卫生重点。然而,很少有研究关注老年性和性别少数群体(SGM)人群之间的这种关联,更不用说关注老年艾滋病毒感染者的独特问题,我们开始在这里填补这一空白。方法:本分析的数据来自哥伦布健康老龄化项目(CHAP),这是一项针对居住在俄亥俄州哥伦布市的≥50岁成年人的横断面调查。使用多变量线性回归模型评估酒精使用(通过AUDIT评分)与几种心理健康结果(如抑郁、焦虑、感知压力和性取向微侵犯)之间的关系,并根据人口统计学特征和其他风险因素进行调整。通过自我报告的艾滋病毒状况来评估模型的适度性。结果:整个样本(N = 787)中,平均感知压力得分为18.2 (SD=5.5),平均焦虑得分为9.1(5.9),平均抑郁得分为9.9 (SD=6.7)。32例(7.4%)自我报告为PLWH。在报告有酒精使用的患者中,平均AUDIT评分为10.5 (SD=10.9)。各心理健康结局指标与审计评分呈正相关。同时,艾滋病毒感染状况对每个心理健康结果指标都有显著的调节作用,这表明在每种情况下,审计评分与心理健康结果指标有更强的关联。结论:我们的研究结果表明,存在广泛的压力因素影响酒精使用,不仅在老年SGM中,而且在PLWH中尤其如此。尽管结果各不相同,但这些数据强调需要对SGM老龄人群,特别是PLWH和性别认同不同的人群进行更多的酒精使用研究。
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引用次数: 0
Analgesic effect of oxytocin in alcohol-dependent male and female rats 催产素对酒精依赖雌雄大鼠的镇痛作用。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-21 DOI: 10.1016/j.alcohol.2024.12.002
John Marendes (Jr.), Marissa A. Muench, Camille L. Young, Amira A. Ghaly, Brendan J. Tunstall

Introduction

Chronic alcohol exposure in humans and rodents causes tolerance to the analgesic effects of alcohol, and enhances pain sensitivity during alcohol withdrawal (i.e., hyperalgesia). The available literature suggests a bidirectional enhancement between chronic alcohol consumption and chronic pain sensitivity. We previously found that oxytocin administration could reduce alcohol consumption in alcohol-dependent rats, and now hypothesize that oxytocin, through analgesic action in the central nervous system, could ameliorate the hyperalgesia induced by alcohol-dependence. To test this hypothesis, we assessed the ability of central and peripheral oxytocin administration to alter thermal (Hargreaves assay) and mechanical (Von Frey assay) pain sensitivity, in male and female rats, made alcohol dependent through repeated cycles of chronic-intermittent ethanol-vapor exposure (CIEV; compared to air-exposed controls).

Methods

Male and female cohorts of Wistar rats were surgically prepared with an ICV cannula and assigned to two groups matched in terms of initial response in the Hargreaves assay. Rats in the alcohol dependent group were exposed to chronic-intermittent alcohol-vapor, while air-exposed control rats were exposed only to room air and served as the control group. The thermal nociception sensitivity of all rats was monitored via weekly Hargreaves assay to determine alcohol-dependence-induced hyperalgesia in dependent rats. Next, rats were ICV administered oxytocin (0, 0.5, or 5 μg in 2.5 μL saline) prior to Hargreaves testing (Experiment 1) or Von Frey testing (Experiment 2). Finally, rats were IP administered oxytocin (0, 0.1, or 1 mg/kg) prior to Hargreaves testing (Experiment 3) or Von Frey testing (Experiment 4). In a follow-up experiment, female rats were tested to directly compare three methods for applying the Von Frey test.

Results

Male and female alcohol-dependent rats developed hyperalgesia, observed in the Hargreaves assay (Experiment 1 & 3), however, hyperalgesia was not so readily observed when the same rats were tested in the Von Frey assay (Experiments 2 & 4, with the exception of female rats in Experiment 4; follow-up testing indicated that the method of Von Frey test employed is likely important to explain this discrepancy). In both the Hargreaves and Von Frey assays, and in both male and female rats, following central or peripheral administration, oxytocin produced analgesia similarly in both alcohol dependent rats and air-exposed controls.

Conclusion

Together, these data suggest the oxytocin system could be targeted to produce therapeutic action in disease that produce hyperalgesia such as in alcohol dependence. We discuss methodological considerations and future experiments that could further elucidate a role for oxytocin in the overlapping neurobiology of alcohol dependence and chronic pain.
人类和啮齿动物的慢性酒精暴露导致对酒精镇痛作用的耐受性,并在酒精戒断期间增强疼痛敏感性(即痛觉过敏)。现有文献表明,慢性酒精消费和慢性疼痛敏感性之间存在双向增强。我们之前发现催产素可以减少酒精依赖大鼠的酒精消耗,现在假设催产素通过中枢神经系统的镇痛作用,可以改善酒精依赖引起的痛觉过敏。为了验证这一假设,我们评估了中枢和外周催产素给药改变雄性和雌性大鼠的热(Hargreaves实验)和机械(Von Frey实验)疼痛敏感性的能力,这些大鼠通过反复循环的慢性间歇性乙醇蒸汽暴露(CIEV;与暴露在空气中的对照组相比)。方法:将Wistar大鼠的雄性和雌性队列用ICV套管进行手术准备,并根据哈格里夫斯试验的初始反应分为两组。酒精依赖组大鼠暴露于慢性间歇性酒精蒸气中,而空气暴露组大鼠仅暴露于室内空气中作为对照组。通过每周哈格里夫斯实验监测所有大鼠的热痛觉敏感性,以确定依赖大鼠的酒精依赖性致痛觉过敏。然后,在Hargreaves实验(实验1)或Von Frey实验(实验2)前,分别在2.5 μL生理盐水中注射催产素(0、0.5或5 μg)。最后,在Hargreaves实验(实验3)或Von Frey实验(实验4)前,用IP给药催产素(0、0.1或1 mg/kg)。在后续实验中,雌性大鼠直接比较三种应用Von Frey实验的方法。结果:哈格里夫斯实验(实验1和3)中观察到,雄性和雌性酒精依赖大鼠出现痛感过敏(实验1和3),然而,Von Frey实验(实验2和4)中对同一只大鼠进行测试时,不容易观察到痛感过敏(实验4中雌性大鼠除外;后续测试表明,Von Frey测试的方法可能对解释这种差异很重要)。在Hargreaves和Von Frey的实验中,在雄性和雌性大鼠中,在中枢或外周给药后,催产素在酒精依赖大鼠和暴露在空气中的对照组中产生了类似的镇痛作用。结论:综上所述,这些数据表明,催产素系统可以针对产生痛觉过敏的疾病(如酒精依赖)产生治疗作用。我们讨论了方法学上的考虑和未来的实验,可以进一步阐明催产素在酒精依赖和慢性疼痛的重叠神经生物学中的作用。
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Alcohol
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