Alcoholic Research Articles

Was receipt of any specialty alcohol treatment during the pandemic effective at reducing drinking for patients with or at risk of AUD?

IntroductionThe COVID-19 pandemic changed the way healthcare providers delivered most health services, including treatment for alcohol use disorder (AUD). Specialty alcohol treatment remained available through the pandemic, and within some systems treatment use increased likely due to telehealth availability. However, the field knows little about the relationship between the pandemic's expanded access to specialty alcohol treatment and alcohol use outcomes. MethodsThe sample included 14,712 patients from Kaiser Permanente Northern California who screened positive for unhealthy alcohol use in primary care and had an AUD diagnosis or risked developing an AUD by reporting 5 or more heavy drinking days in a 3-month period between 1/1/2019 and 2/29/2020 (pre-pandemic). The study examined the receipt of any specialty alcohol treatment (including at least one outpatient, inpatient, or telehealth specialty treatment encounter, or pharmacotherapy prescription) from 3/1/2020 (pandemic start) to either the first completed follow-up alcohol screening or 6/20/2022 (study period end). The outcomes of alcohol use included changes in heavy drinking days, drinks per week, drinking days per week, and drinks per drinking day between the pre- and post-pandemic periods. ResultsOn average patients significantly decreased alcohol use across all four alcohol use measures examined, regardless of whether they received treatment. However, those who received any treatment compared to those who did not had greater reductions in alcohol use, with an additional decrease of −3.55 heavy drinking days (95 % CI = −5.93, −1.17), −3.80 drinks per week (95 % CI = −5.18, −2.42), −0.72 drinks per drinking day (95 % CI = −1.14, −0.30), and − 1.01 drinking days per week (95 % CI = −1.30, −0.72). Treatment effects were greatest among patients who exceeded both daily and weekly limits pre-pandemic, with an additional decrease of −10.75 heavy drinking days (95 % CI = −15.28, −6.21), −12.83 drinks per week (95 % CI = −16.31, −9.35), −1.67 drinks per drinking day (95 % CI = −2.19, −1.14), and −2.02 drinking days per week (95 % CI = −2.41, −1.63). ConclusionsOn average, patients decreased alcohol use during the onset of the pandemic, however, those who had any specialty alcohol treatment had significantly greater decreases, suggesting that the hybrid in-person and telehealth treatment approach was effective during the pandemic.

Trends of fully alcohol-attributable mortality rates before and during COVID-19 in the Baltic and other European countries.

We tested the polarization hypothesis, which postulates that during times of crises, such as the COVID-19 pandemic, alcohol consumption increases among the heaviest drinkers but decreases among most other drinkers, resulting in an overall decrease in consumption among the population. We posited the increase in heavy drinking would lead to increases in 100% alcohol-attributable (AA) mortality. Furthermore, based on the high level of alcohol consumption in the Baltic countries compared to other European countries, we predicted that the increases in AA mortality would be more pronounced in these countries. Data for 100% AA deaths were obtained from the World Health Organization for the period 2010 to 2022, and standardized to the regional age distribution for 2010. Parametric and non-parametric tests were used to test the study hypotheses. The mean age-standardized 100% AA mortality rate increased during the COVID-19 pandemic in the 19 European countries with data by 3.12 deaths per 100,000 population, constituting an 18% increase (tested against no change: t = 2.52; df = 18; p = 0.021). This increase was higher in the Baltic countries (mean difference = 13.41 deaths per 100,000 population; standard deviation (SD) = 7.44; 46% increase) than for other European countries (mean difference = 1.19; SD = 1.55; 8% increase). The increases in 100% AA mortality were associated with decreases in the level of alcohol consumption in the majority of countries. As predicted, 100% AA mortality increased in 19 European countries during the COVID-19 pandemic, with the Baltic countries seeing a higher increase. Renewed alcohol control policy efforts should be considered.

Domiciliary Carers' Perspectives on Alcohol Use by Older Adults in Their Care: A Systematic Review and Thematic Synthesis of Qualitative Studies.

As global populations continue to age, alcohol consumption rises, and we strive to age in place, it is important to have an up-to-date understanding of domiciliary carers' perspectives on older adults' alcohol use in their care. Therefore, a systematic review and thematic synthesis of qualitative studies of the unique challenges faced by domiciliary care workers in front line roles regarding older adults' alcohol use was conducted (PROSPERO registration number: CRD42024516660). Eight databases were searched on 22 February 2024 for qualitative studies focusing on older adults' (defined as aged 50 or over) alcohol consumption and domiciliary care. The Critical Appraisal Skills Programme checklist was utilised for quality appraisal. Twenty articles reporting 14 unique studies of mainly medium to low quality were included. Three overarching themes (and associated subthemes) were identified as follows: identification (alcohol problems are common, no assessment for alcohol problems, and additional overt signs of excessive alcohol use), management (to buy or not to buy that is the question, balancing rights and risks, monitor and report but do not intervene, maintaining the vicious circle, home as a barrier to accessing support and services, and more support needed from healthcare professionals), and training (lack of alcohol education). Domiciliary carers are well placed to make every contact count to target alcohol consumption but would benefit from support and resources for alcohol consumption identification and management. Clear guidance on how to manage alcohol consumption to harmoniously balance rights and risks is crucial, particularly when caring for older adults with cognitive difficulties.

Mapping the Fetal Alcohol Spectrum Disorder Continuum of Care Across the Military Health System.

Although a leading cause of developmental disability in the United States, many individuals with fetal alcohol spectrum disorders (FASDs) do not receive a timely diagnosis, are misdiagnosed, or are never diagnosed. Prevention, diagnosis, and clinical management of FASD have not been previously studied in the U.S. Military Health System (MHS), where nearly 1 million of the nation's children receive health care. To address this gap, we undertook an environmental scan of the clinical guidelines, services, programs, educational resources, and policies within the MHS pertaining to alcohol use (AU), AU disorder (AUD), prenatal alcohol exposure, and FASD. From March to June 2023, we undertook an environmental scan of MHS clinical guidelines, services, programs, educational resources, and policies that address AU, AUD, prenatal alcohol exposure, and FASD. We identified multiple resources that attended to AU and AUD before and during pregnancy in the MHS. However, despite numerous resources for other neurodevelopmental disorders, we did not find any MHS-specific resources that address diagnosis and management of FASD. Findings suggest opportunities to raise awareness, educate providers, and improve guidelines, policies, and practices in the MHS.

Machine learning and Bayesian network analyses identifies associations with insomnia in a national sample of 31,285 treatment-seeking college students

BackgroundA better understanding of the relationships between insomnia and anxiety, mood, eating, and alcohol-use disorders is needed given its prevalence among young adults. Supervised machine learning provides the ability to evaluate which mental disorder is most associated with heightened insomnia among U.S. college students. Combined with Bayesian network analysis, probable directional relationships between insomnia and interacting symptoms may be illuminated.MethodsThe current exploratory analyses utilized a national sample of college students across 26 U.S. colleges and universities collected during population-level screening before entering a randomized controlled trial. We used a 4-step statistical approach: (1) at the disorder level, an elastic net regularization model examined the relative importance of the association between insomnia and 7 mental disorders (major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, post-traumatic stress disorder, anorexia nervosa, and alcohol use disorder); (2) This model was evaluated within a hold-out sample. (3) at the symptom level, a completed partially directed acyclic graph (CPDAG) was computed via a Bayesian hill-climbing algorithm to estimate potential directionality among insomnia and its most associated disorder [based on SHAP (SHapley Additive exPlanations) values)]; (4) the CPDAG was then tested for generalizability by assessing (in)equality within a hold-out sample using structural hamming distance (SHD).ResultsOf 31,285 participants, 20,597 were women (65.8%); mean (standard deviation) age was 22.96 (4.52) years. The elastic net model demonstrated clinical significance in predicting insomnia severity in the training sample [R2 = .44 (.01); RMSE = 5.00 (0.08)], with comparable performance in the hold-out sample (R2 = .33; RMSE = 5.47). SHAP values indicated that the presence of any mental disorder was associated with higher insomnia scores, with major depressive disorder as the most important disorder associated with heightened insomnia (mean |SHAP|= 3.18). The training CPDAG and hold-out CPDAG (SHD = 7) suggested depression symptoms presupposed insomnia with depressed mood, fatigue, and self-esteem as key parent nodes.ConclusionThese findings provide insights into the associations between insomnia and mental disorders among college students and warrant further investigation into the potential direction of causality between insomnia and depression.Trial registrationTrial was registered on the National Institute of Health RePORTER website (R01MH115128 || 23/08/2018).

Rejecting Identities: Stigma and Hermeneutical Injustice

ABSTRACT Hermeneutical injustice means being unjustly prevented from making sense of one’s experiences, identity or circumstances and/or communicating about them. The literature focusses almost exclusively on whether people have access to adequate conceptual resources. In this paper, we discuss a different kind of hermeneutical struggle caused by stigma. We argue that in some cases of hermeneutic injustice people have access to hermeneutical resources apt to understand their identity but reject employing these due to the stigma attached to the identity. We begin with a reinterpretation of one of the cases discussed in the literature, Edmund White’s novel A Boy’s Own Story. We argue that in this case hermeneutic resources are available but are rejected due to the stigma attached to homosexuality. We then present two analogous kinds of cases: alcohol addiction and being the victim of intimate partner violence. Here, too, hermeneutic injustice occurs because of the stigma attached to an identity rather due to unavailability of resources. We close by suggesting that these cases may, additionally, involve the wrong of ‘Tightlacing’: by meddling with their self-conception, stigma can manipulate individuals into a view of themselves that licenses inappropriate demands on them and makes them complicit in the erasure of their identities.

Role of Imaging in Screening for Hepatocellular Carcinoma.

Primary liver cancer is among the most common cancers globally. It is the sixth-most common malignancy encountered and the third-most common cause of cancer-related death. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for about 90% of primary liver cancers. The majority of HCCs occur in patients with underlying cirrhosis, which results from chronic liver diseases such as fatty liver, hepatitis B and hepatitis C infections, and chronic alcohol use, which are the leading causes. The obesity pandemic has led to an increased prevalence of nonalcoholic fatty liver disease (NAFLD), which leads to nonalcoholic steatohepatitis and could progress to cirrhosis. As HCC is among the most common cancers and occurs in the setting of chronic liver disease in most patients, screening the population at risk could help in early diagnosis and management, leading to improved survival. Screening for HCC is performed using biochemical marker testing such as α-fetoprotein (AFP) and cross-sectional imaging. It is critical to emphasize that HCC could potentially occur in patients without cirrhosis (non-cirrhotic HCC), which can account for almost 20% of all HCCs. The lack of cirrhosis can cause a delay in surveillance, which could potentially lead to diagnosis at a later stage, worsening the prognosis for such patients. In this article, we discuss the diagnosis of cirrhosis in at-risk populations with details on the different modalities available for screening HCC in patients with cirrhosis, emphasizing the role of abdominal ultrasounds, the primary imaging modality in HCC screening.

Sleep Characteristics Among Children with a Parental History of Alcohol Use Disorder

Abstract Purpose of Review The purpose of the review was to examine findings on sleep characteristics among children with a parental history of alcohol use disorder (CPHAUDs) in different age groups. We identified unanswered questions and discussed directions for future research. We also discussed the implications of these current findings on alcohol prevention and intervention programs. Recent Findings Parental ratings and youth report of sleep difficulties have been longitudinally associated with the emergence of alcohol use and alcohol-related problems among both CPHAUDsand non-CPHAUDs. There were inconsistent findings comparing sleep characteristics in these two groups. Studies that used self-report and parental ratings reported no or minimal differences while studies that used actigraphy and polysomnography found significant, albeit moderate but meaningful differences. Summary Current research shows that CPHAUDs and non-CPHAUDs are similar on most objective and subjective sleep measures. There are a few significant differences between the two groups that may have implications for the development of behavioral problems, substance use and other risk behaviors.

The role of alcohol consumption in the lives of older Australian women: qualitative insights and an agenda for further research, policy and practice

BackgroundAlcohol consumption presents a threat to the health and wellbeing of women. The alcohol industry often pushes back at global efforts to prioritise the prevention of alcohol harms to women. Qualitative researchers have investigated how younger and midlife women conceptualise their alcohol consumption, but there is very limited research relating to older women (those 60 years and over).MethodsUsing data collected from an online qualitative survey, this paper explored the factors that influence how older Australian women drinkers (n = 144. 60–88 years) conceptualised the role of alcohol in their lives. The study used a ‘Big Q’ reflexive approach to thematic analysis, drawing upon sociological theories of risk and symbolic interactionism to construct four themes from the data.ResultsFirst, alcohol consumption was viewed by participants as an accepted and normalised social activity, that was part of Australian culture. Second, alcohol played a role for some participants as a way to cope with life changes (such as retirement), as well as managing stressful or challenging life circumstances (such as loneliness). Third, alcohol was part of the routines and rituals of everyday life for some women. For example, women discussed the consumption of wine with their evening meal as an important part of the structure of their day. Fourth, participants had clear personal expectancies about what it meant to be a ‘responsible drinker’. They had clear narratives about personal control and moral obligation, which in some cases created a reduced perception of their own risk of alcohol-caused harm.ConclusionsThis research provides a starting point for future public health research examining the factors that may shape older women’s alcohol consumption beliefs and practices. Public health activities should consider the unique needs and potential vulnerabilities of older women drinkers, and how these may be potentially exploited by the alcohol industry.

Assisted resolution and self-change: differences between healthcare systems.

This editorial discusses a study by Day and colleagues, in which the authors investigated the prevalence of resolution of alcohol and other drug problems in the UK and compared people who resolved their problems with and without treatment.

A Case Report of Bacterial Meningoencephalitis with Altered Sensorium in a 50-Year-Old Male

Bacterial meningoencephalitis remains a significant cause of morbidity and mortality worldwide, requiring prompt diagnosis and treatment. We present a case of a 50-year-old male who presented to the emergency room with a three-day history of low-grade fever, chills, altered sensorium, and recent episodes of seizures. Upon admission, the patient demonstrated positive Kernig's sign, bilateral pinpoint pupils, incomprehensible speech, and drowsiness, with a Glasgow Coma Scale score of E3M5V2. The patient had a significant history of chronic alcohol consumption spanning 32 years. Cerebrospinal fluid analysis revealed elevated protein levels (79.7 mg/dL) and the presence of Streptococcus pyogenes in culture, confirming the diagnosis of bacterial meningoencephalitis. While neuroimaging studies, including MRI and CT scan, showed no significant abnormalities, other diagnostic tests helped rule out concurrent infections. The patient received empirical antibiotic therapy with intravenous ceftriaxone, along with acyclovir, vancomycin, and supportive medications. Treatment also included management of increased intracranial pressure, seizure control, and careful monitoring of neurological status. Following a comprehensive 16-day treatment regimen, the patient showed significant improvement and was discharged in stable condition. This case shows the importance of early recognition of symptoms, prompt initiation of appropriate antimicrobial therapy, and the need for a multidisciplinary approach in managing bacterial meningoencephalitis. Regular follow-up was recommended due to the risk of relapse and potential long-term complications

Choice of alcohol over a natural reward: an experimental study in light and heavy social drinkers.

A core symptom of alcohol use disorder (AUD) is a progressively increased choice of alcohol over alternative rewards despite negative consequences. Here, we investigated choice between personalized alcohol vs. natural rewards in a laboratory setting, and compared this behavior between non-treatment-seeking heavy drinkers and light social drinkers. 30 light social drinkers (15 men drinking < 15 drinks/week and 15 women drinking < 10 drinks/week) and 30 heavy, non-treatment-seeking drinkers (drinking more than these levels; 15 women). In the Concurrent Choice Alcohol Food (CCAF) task, participants chose between individually tailored images of alcohol and snack rewards and collected points towards the respective reward. To assess cost sensitivity, points associated to the images varied so that they favored alcohol or snack, or were equal, creating three relative point levels. Choice preference for alcohol was strongly correlated with Alcohol Use Disorder Identification Test (AUDIT) scores, supporting the external validity of the choice procedure. Compared to light drinkers, heavy drinkers showed increased choice preference for alcohol, as indicated by a between-group difference in points of subjective equality, a metric that quantifies the relative point level at which alcohol and snacks were equally likely to be chosen. In both groups, choice preference strongly depended on the relative point level of alcohol compared to snacks, suggesting that responding for alcohol in heavy drinkers was sensitive to costs. Our results replicate previous findings of a relationship between self-reported alcohol use and choice preference for alcohol. We also found that choice behavior was strongly dependent on relative cost of alcohol in both groups, although price sensitivity was lower in heavy compared to light drinkers. An increased choice preference for alcohol in heavy drinkers suggests that they attribute a higher relative reinforcing value to alcohol compared to natural rewards.

BEHAVIORAL IMPACTS ASSOCIATED WITH DRINKING IN AMAZON ETHNICS: A systematic review of the literature

The objective of this work is to prove the presence of disruptive behaviors due to excessive alcohol consumption by indigenous peoples. Having as a theoretical methodological contribution the carrying out of a systematic literature review, with bibliographical research being carried out through the gathering of articles found in the Google Scholar databases, CAPES journal portal and Scielo platform, published between the years 2019 and 2023 After a structured analysis of the literature review, 20 articles were selected to prepare this article. However, a significant gap in specific studies on the topic was found, which made it difficult to obtain objective results. Despite this limitation, the systematic analysis of the literature allowed a broader understanding of the problem of alcoholism in the Brazilian indigenous population. Alcohol consumption among indigenous peoples is recognized as a complex and multifaceted problem, influenced by the cultural and linguistic diversity of communities, as well as variations in consumption rates between different regions and ethnic groups. This excessive consumption has significant negative impacts on physical and mental health, social cohesion and is associated with other public health problems. Although public policies and specific interventions, such as the National Mental Health Policy, are important in addressing this problem, they face significant challenges in implementation. Therefore, integrated and culturally sensitive approaches are essential to effectively address the problem of alcohol consumption among indigenous peoples in Brazil.

Menopause and Sexual Life Amongst Older Men: A Review Study

Objectives: To determine factors affecting the quality of men’s sexual life during menopause and identify the existing challenges. Design: A review study. Setting(s): Older people living in public institutions and living in their own homes. Participants: Older adults over 60 years of age. Outcome measures: All factors affecting the quality of sexual life of postmenopausal men in old age have been investigated in three physical, psycho-emotional, and social domains. Results: In the physical field, factors such as age, general health, disease, exercise, impotence, erectile dysfunction, genital warts, surgery of total hip arthroplasty, surgery of prostate, cancer radiotherapy, alopecia, and disorder in ejaculation, urinary disorders, and physical rehabilitation were known factors affecting the quality of men’s sexual life. The impacts of factors such as sleep problems, stressors, self-image, depression, alcohol addiction, premature ejaculation, emotional divorce, marital satisfaction, and fear of sexual activity were confirmed in the psycho-emotional field of studies. In the social field, factors such as education, duration of the marriage, marital status, income, life partners, number of sexual relations with spouse, the presence of multiple sexual partners, body mass of spouse (female), sex education and health literacy, sexual awareness, and quality of life related to health were recognized to be effective. Conclusions: Promoting sexual awareness through educational programs, providing opportunities for frequent sexual relationships, and addressing physical, psychological, emotional, cognitive, and social factors, and andropause could contribute to a more desirable sexual life quality in men during andropause.

Chronic alcohol consumption aggravates acute kidney injury through integrin β1/JNK signaling

Alcohol abuse is one of the major public health problems in the world and is associated with various health conditions. However, little is known about the effect of alcohol consumption on acute kidney injury (AKI). In this study, we demonstrate that chronic and binge alcohol feeding with a Lieber-DeCarli diet containing 5 % ethanol for 10 days, followed by a single dose of 31.5 % ethanol by gavage, aggravated AKI after ischemia-reperfusion injury (IRI) in female, but not in male, mice. Kidney dysfunction, histopathology and tubular cell apoptosis were more severe in EtOH-fed female mice after IRI, compared to pair-fed controls. RNA sequencing and experimental validation uncovered that activation of integrin β1 and its downstream c-Jun NH2-terminal kinase (JNK) aggravated AKI in EtOH-fed mice. Knockdown of integrin β1 inhibited JNK phosphorylation and alleviated AKI in EtOH-fed mice, whereas activation of integrin β1 by agonist antibody increased JNK phosphorylation, worsened renal histological injury and tubular cell apoptosis, and aggravated kidney dysfunction. In vitro, activation of integrin β1 increased JNK phosphorylation and induced tubular epithelial cell apoptosis. The detrimental effect of EtOH feeding was primarily mediated by acetaldehyde, as its levels were increased in the blood, liver and kidney of female mice fed with ethanol. Acetaldehyde per se activated integrin β1/JNK signaling and induced tubular cell apoptosis in vitro. These findings suggest that alcohol consumption increases vulnerability to AKI in female mice, which is probably mediated by acetaldehyde/integrin β1/JNK signaling cascade.

Tackling hospital service burden of alcohol dependence in England: a service evaluation of alcohol care teams (ACTs) and care pathways for integrated care

Background Chronic alcohol disorder hospital admissions are increasing in England and present a huge cost to England’s health and social care costs. Hospital-based alcohol care teams (ACTs) aim to better meet these patients’ complex needs through assessment and targeted referral. This has the potential to work effectively within England’s newly established integrated care system. Methods The aim of this project was to identify in what ways ACTs can be effective in improving care pathways for complex care in a whole-system health and social care setting. We conducted semi-structured, tailored interviews with practitioners, managers and commissioners, across three hospital and community settings in one large urban region in England, comparing ACT working with non-ACT working. Results Effective pathways were enabled by the presence of an ACT, multi-agency community initiatives, assertive alcohol outreach and frequent-attender team meetings. Identified barriers were lack of systemic funding and commissioning, poor communication between agencies, lack of information-sharing and insufficient staff training. Conclusion Community outreach and in-reach between hospitals and community services enable effective care pathways when ACTs provide the point of contact. A well-resourced ACT with clear operational remit can create links between diverse agencies and enables improved wraparound care for alcohol dependent patients.

Multidimensional fluorescence spectroscopic characterization of Spain’s top-selling gins: Category and alcohol content

Excitation-emission fluorescence spectroscopy (EEFS) is emerging as a powerful tool for food characterization and authentication. This study pioneers the use of EEFS to characterize and differentiate Spain’s top-selling gins, considering categories and alcohol content. Twenty gins, including alcoholic (ALC), light alcoholic (LIG), and non-alcoholic (NALC) types, were analyzed generating excitation-emission matrices (EEMs), which were processed with multi-way principal component analysis (MPCA) and PARAllel FACtor analysis (PARAFAC). Results revealed distinct spectral fingerprints for each gin type, with significant differences between alcoholic and non-alcoholic gins. Light gins closely resembled their full-alcohol counterparts, indicating minimal alteration in gin characteristics due to reduced alcohol content, while non-alcoholic gins showed substantial divergence. The MPCA model highlighted primary differences between ALC and NALC types, while the PARAFAC models identified specific fluorophores linked to juniper berries and other botanicals. This study confirms that EEFS, coupled with chemometrics, is effective in authenticating gin products, marking a significant advancement in spirit analysis.

Centrally administered growth hormone secretagogue receptor antagonist DLys decreases alcohol intake and preference in male mice.

Alcohol use disorder (AUD) is a highly prevalent public health problem. The ghrelin system has been identified as a potential target for therapeutic intervention for AUD. Previous work showed that systemic administration of the growth hormone secretagogue receptor (GHSR) antagonist DLys reduced alcohol intake and preference in male mice. Yet, it is unclear whether central or peripheral GHSRs mediated these effects. We hypothesized that alcohol consumption is driven by central GHSRs and addressed this hypothesis by testing the effects of central administration of DLys. Male C57BL/6J mice consumed alcohol in a two-bottle choice procedure (10% ethanol versus water). DLys (2 nmol) was administered intracerebroventricularly for 7 days to examine alcohol intake and preference. DLys decreased alcohol intake and preference but had no effect on food intake. The effects on alcohol intake and preference persisted after several administrations, indicating lack of tolerance to DLys' effects. These results suggest that central administration of DLys is sufficient to reduce alcohol drinking and that DLys remains effective after several administrations when given intracerebroventricularly. Moreover, this work suggests that the effects of intracerebroventricularly administered DLys are specific to alcohol and do not generalize to other calorie-driven behaviors.

LEAP2, a ghrelin receptor inverse agonist, and its effect on alcohol-related responses in rodents

The underlying neurobiology of alcohol use disorder (AUD) is complex and needs further unraveling, with one of the key mechanisms being the gut-brain peptide ghrelin and its receptor (GHSR). However, additional substrates of the ghrelin pathway, such as liver-expressed antimicrobial peptide 2 (LEAP2), an endogenous GHSR inverse agonist, may contribute to this neurobiological framework. While LEAP2 modulates feeding and reward through central mechanisms, its effects on alcohol responses are unknown. The aim of the present study was therefore to identify the impact of central LEAP2 on the ability of alcohol to activate the mesolimbic dopamine system and to define its ability to control alcohol intake. These experiments revealed that central LEAP2 (i.e. into the third ventricle) prevented the ability of alcohol to cause locomotor stimulation in male mice, suppressed the memory of alcohol reward and attenuated the dopamine release in the nucleus accumbens caused by alcohol. Moreover, central LEAP2 reduced alcohol consumption in both male and female rats exposed to alcohol for 6 weeks before treatment. However, the serum levels of LEAP2 were similar between high- and low- alcohol-consuming (male) rats. Furthermore, central LEAP2 lowered the food intake in the alcohol-consuming male rats and reduced the body weight in the females. Collectively, the present study revealed that central LEAP2 mitigates alcohol-related responses in rodents, contributing to our understanding of the ghrelin pathway’s role in alcohol effects.

Adaptations in glutathione-based redox protein signaling pathways and alcohol drinking across species

Alcohol use disorder (AUD) is the most prevalent substance use disorder but there is incomplete knowledge of the underlying molecular etiology. Here, we examined the cytosolic proteome from the nucleus accumbens core (NAcC) of ethanol drinking rhesus macaques to identify ethanol-sensitive signaling proteins. The targets were subsequently investigated using bioinformatics, genetic, and pharmacological manipulations in mouse models of ethanol drinking. Of the 1000+ cytosolic proteins identified in our screen, 50 proteins differed significantly between control and ethanol drinking macaques. Gene Ontology analysis of the differentially expressed proteins identified enrichment in pathways regulating metabolic processes and proteasome activity. Because the family of Glutathione S-transferases (GSTs) was enriched in these pathways, validation studies targeted GSTs using bioinformatics and genetically diverse mouse models. Gstp1 and Gstm2 were identified in Quantitative Trait Loci and published gene sets for ethanol-related phenotypes (e.g., ethanol preference, conditioned taste aversion, differential expression), and recombinant inbred strains that inherited the C57BL/6J allele at the Gstp2 interval consumed higher amounts of ethanol than those that inherited the DBA/2J allele. Genetic deletion of Gstp1/2 led to increased ethanol consumption without altering ethanol metabolism or sucrose preference. Administration of the pharmacologic activator of Gstp1/2, carnosic acid, decreased voluntary ethanol drinking. Proteomic analysis of the NAcC cytosolic of heavy drinking macaques that were validated in mouse models indicate a role for glutathione-mediated redox regulation in ethanol-related neurobiology and the potential of pharmacological interventions targeting this system to modify excessive ethanol drinking.