scholarly journals Toll-like receptor 3 activation increases voluntary alcohol intake in C57BL/6J male mice

2018 ◽  
Author(s):  
Anna S. Warden ◽  
Moatasem M. Azzam ◽  
Adriana DaCosta ◽  
Sonia Mason ◽  
Yuri A. Blednov ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
Alcohol Intake ◽  
Drinking Behavior ◽  
Ethanol Exposure ◽  
Innate Immune ◽  
Poly I:C ◽  
List Type ◽  
Toll Like Receptor ◽  
Excessive Alcohol

AbstractMany genes differentially expressed in brain tissue from human alcoholics and animals that have consumed large amounts of alcohol are components of the innate immune toll-like receptor (TLR) pathway. TLRs initiate inflammatory responses via two branches: (1) MyD88-dependent or (2) TRIF-dependent. All TLRs signal through MyD88 except TLR3. Prior work demonstrated a direct role for MyD88-dependent signaling in regulation of alcohol consumption. However, the role of TLR3 as a potential regulator of excessive alcohol drinking has not previously been investigated. To test the possibility TLR3 activation regulates alcohol consumption, we injected mice with the TLR3 agonist polyinosinic:polycytidylic acid (poly(I:C)) and tested alcohol consumption in an every-other-day two-bottle choice test. Poly(I:C) produced a persistent increase in alcohol intake that developed over several days. Repeated poly(I:C) and ethanol exposure altered innate immune transcript abundance; increased levels of TRIF-dependent pathway components correlated with increased alcohol consumption. Administration of poly(I:C) before exposure to alcohol did not alter alcohol intake, suggesting that poly(I:C) and ethanol must be present together to change drinking behavior. To determine which branch of TLR signaling mediates poly(I:C)-induced changes in drinking behavior, we tested either mice lacking MyD88 or mice administered a TLR3/dsRNA complex inhibitor. MyD88 null mutants showed poly(I:C)-induced increases in alcohol intake. In contrast, mice pretreated with a TLR3/dsRNA complex inhibitor reduced their alcohol intake, suggesting poly(I:C)-induced escalations in alcohol intake function are, at least partially, dependent on TLR3. Together, these results strongly suggest that TLR3-dependent signaling drives excessive alcohol drinking behavior.HighlightsActivation of TLR3 via poly(I:C) increased alcohol intake.Poly(I:C) and ethanol must be present together to change drinking behavior.Increased alcohol intake due to poly(I:C) is independent of MYD88.Increased alcohol intake due to poly(I:C) is dependent on TLR3.

scholarly journals Changes in Alcohol Consumption Among a Population Who Underwent Medical Checkups During the First Wave of the Coronavirus Disease 2019 Pandemic in Japan: A Single-Center Retrospective Study

2022 ◽  
Vol 22 (3) ◽  
pp. 169-173
Author(s):  
Yusaku Kajihara
Keyword(s):  
Retrospective Study ◽  
Alcohol Consumption ◽  
Alcohol Intake ◽  
Drinking Behavior ◽  
Limited Information ◽  
Excessive Alcohol Consumption ◽  
Excessive Alcohol ◽  
Male Sex ◽  
Lifestyle Related Diseases

Background: Movement restrictions during the coronavirus disease 2019 (COVID-19) pandemic have inflicted stress and affected drinking behavior. However, limited information is available on the changes in alcohol use among the Japanese population.Method: This retrospective study included 371 subjects aged 20–74 years who underwent medical checkups at Fuyoukai Murakami Hospital before (April 1, 2019 to December 31, 2019) and during the COVID-19 pandemic (April 1, 2020 to May 31, 2020). All data were extracted from medical records. Changes in alcohol consumption and severity were also investigated. A logistic regression model was used to identify the risk factors associated with increased drinking, and seven variables were sequentially introduced into the model—age (≤ 49 years), male sex, prior instructions for alcohol restriction, medication for lifestyle-related diseases (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, and hyperuricemia), depression or insomnia, essential workers, and smoking.Results: The median age was 46 years, and 81.7% subjects were men. In total, 25.1% subjects increased their alcohol intake, and 24.5% subjects reduced their alcohol intake. The rates of excessive alcohol consumption (≥ 60 g ethanol per day) were 15.9% and 16.7% in the pre-COVID-19 period and during the COVID-19 pandemic, respectively. Multivariate analysis identified only age ≤ 49 years as a risk factor for increased drinking (adjusted odds ratio, 2.20; 95% confidence interval, 1.22–3.99; p = 0.009).Conclusion: Approximately one-fourth of the subjects reported increased drinking, although the overall severity remained stable. The importance of alcohol reduction, particularly among young people, should be emphasized.

Abstract P158: Systematic Review and Meta-analysis of Acute Effects of Alcohol Consumption on Risk of Cardiovascular Events

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Elizabeth Mostofsky ◽  
Harpreet S Chahal ◽  
Kenneth J Mukamal ◽  
Eric B Rimm ◽  
Murray A Mittleman
Keyword(s):  
Cardiovascular Risk ◽  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
Lower Risk ◽  
Cardiovascular Events ◽  
Alcohol Intake ◽  
Meta Analysis ◽  
Moderate Alcohol Consumption ◽  
Consistent Finding ◽  
Heavy Alcohol

Introduction: Although considerable research describes the cardiovascular effects of habitual moderate and heavy alcohol consumption, the acute risks following alcohol intake have not been well characterized. Based on its physiological effects, alcohol may have markedly different effects on acute and long-term risk. We assessed the hypothesis that moderate alcohol consumption is associated with an immediately higher risk of cardiovascular events that becomes protective after 24 hours, whereas heavy alcohol drinking is associated with higher cardiovascular risk both immediately and in the following days. Methods: We searched CINAHL, Embase, PubMed and PsycINFO from inception to March 12 2015, supplemented with manual screening for observational studies assessing the association between alcohol intake and cardiovascular events in the following hours and days. We calculated pooled relative risks (RRs) and 95% confidence intervals (CIs) for the association between alcohol intake and myocardial infarction (MI), ischemic stroke (IS) and hemorrhagic stroke (HS) using DerSimonian and Laird random-effects models to model any alcohol intake or dose-response relationships of alcohol intake and cardiovascular events. Results: Among 1056 citations and 37 full-text articles reviewed, 23 studies (29457 participants) were included. Moderate alcohol consumption was associated with an acutely higher cardiovascular risk that was attenuated after 24 hours and even protective for MI and HS (≈2-4 drinks: RR=30% lower risk), and protective against IS within one week (≈6 drinks: RR=19% lower risk). In contrast, heavy alcohol drinking was associated with higher cardiovascular risk in the following day (≈6-9 drinks: RR=1.3-2.3) and week (≈19-30 drinks: RR=2.25-6.2). Conclusions: In conclusion, there appears to be a consistent finding of an acutely higher cardiovascular risk following any alcohol consumption but by 24 hours, only heavy alcohol intake conferred continued risk.

scholarly journals Behavioral and Neurobiological Consequences of Hedonic Feeding on Alcohol Drinking

2020 ◽  
Vol 26 (20) ◽  
pp. 2309-2315 ◽  
Author(s):  
Julianna Brutman ◽  
Jon F. Davis ◽  
Sunil Sirohi
Keyword(s):  
Alcohol Drinking ◽  
Alcohol Intake ◽  
Energy Homeostasis ◽  
Drugs Of Abuse ◽  
Drinking Behavior ◽  
The Body ◽  
Alcohol And Drugs ◽  
Signaling Mechanisms ◽  
Functional Consequences ◽  
Neuropsychiatric Conditions

A complex interplay of peripheral and central signaling mechanisms within the body of an organism maintains energy homeostasis. In addition, energy/food intake is modified by various external factors (e.g., palatability, food availability, social and environmental triggers). Highly palatable foods can provoke maladaptive feeding behavior, which in turn disrupts normal homeostatic regulation resulting in numerous health consequences. Furthermore, neuroendocrine peptides, traditionally considered to regulate appetite and energy homeostasis, also control the intake and reinforcing properties of alcohol and drugs of abuse. Therefore, dysregulated eating as a result of a hedonic/binge-like intake of hyper-palatable food may impact alcohol drinking behavior. Relevant in this case is the fact that eating disorders are highly comorbid with several neuropsychiatric conditions, including alcohol use disorder. The present review is intended to summarize the neurobiological and functional consequences of hedonic feeding on alcohol intake.

Is carbohydrate-deficient transferrin in serum useful for detecting excessive alcohol consumption in hypertensive patients?

1994 ◽  
Vol 40 (11) ◽  
pp. 2057-2063 ◽  
Author(s):  
B Fagerberg ◽  
S Agewall ◽  
A Berglund ◽  
M Wysocki ◽  
P A Lundberg ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Intake ◽  
High Alcohol ◽  
Clinical Value ◽  
Excessive Alcohol Consumption ◽  
Cross Sectional ◽  
Hypertensive Patients ◽  
Carbohydrate Deficient Transferrin ◽  
Excessive Alcohol ◽  
High Alcohol Intake

Abstract The aim of this study was to examine the diagnostic usefulness of carbohydrate-deficient transferrin (CDT) in serum in a cross-sectional study of 439 treated hypertensive men. We related the results to alcohol intake by questionnaire and to biochemical and hemodynamic measurements known to reflect excessive alcohol consumption. The diagnostic sensitivity and the specificity for high alcohol intake (> or = 24 g/day of ethanol) were 44% and 87%, respectively. The group with reported high alcohol intake (n = 32) was characterized by hemodynamic and biochemical changes typical of alcohol abuse. The corresponding profile for the patients with increased serum CDT concentrations (n = 70) was different in several respects, indicating a considerable number of false-positive tests. We conclude that serum CDT determination had low sensitivity and specificity for excessive alcohol consumption in this group of hypertensive patients. The results illustrate the importance of evaluating new laboratory methods in unselected patient populations before drawing any conclusions about their clinical value.

scholarly journals Mechanisms underlying controlled alcohol consumption: nociceptine/kappa-opioid related gene expression in the rat brain

2018 ◽  
pp. 112-114
Author(s):  
Ф.Ш. Шагиахметов ◽  
И.Ю. Шамакина ◽  
Т.В. Давыдова
Keyword(s):  
Gene Expression ◽  
Alcohol Consumption ◽  
Alcohol Intake ◽  
Mrna Levels ◽  
Kappa Opioid ◽  
Reward Circuitry ◽  
Free Choice Trial ◽  
Male Wistar Rats ◽  
Excessive Alcohol ◽  
Polymerase Chain

Каппа-опиоидная и ноцицептиновая системы играют важную роль в модуляции функций дофаминергической системы «награды», однако их роль в механизмах формирования аддиктивного поведения до конца не ясна. Цель исследования: сравнить уровни мРНК каппа-опиоидного (OPRK1) и ноцицептинового (OPRL1) рецепторов, а также их эндогенных лигандов - препродинорфина (PDYN) и препроноцицептина (PDYN) в мозге животных с различным уровнем предпочтения алкоголя. Методы: потребление алкоголя у половозрелых крыс-самцов Wistar регистрировали с 60-го по 85-й дни жизни в модели «свободный выбор» между водой и 10% раствором этанола. Относительный уровень мРНК в структурах мозга определяли на 86-й день жизни методом ПЦР в реальном времени. Результаты: Экспрессия мРНК PDYN и PNOC в стриатуме, и OPRK1 и OPRL1 в миндалине была достоверно выше у «отвергающих», т.е. контролирующих потребление алкоголя на постоянно низком уровне животных, по сравнению с «предпочитающими», увеличившими потребление алкоголя в течение эксперимента. Заключение: более высокий уровень экспрессии генов эндогенных опиоидов PDYN и PNOC и их рецепторов в исследованных областях мозга может обусловливать меньшую гедоническую привлекательность алкоголя, играя превентивную роль и снижая риск злоупотребления алкоголем Kappa-opioidergic and nociceptinergic systems both inhibit the mesolimbic reward circuitry but their role in mechanisms of addictive behavior still is not well understood. Objective of the study was to compare expression of kappa opioid and nociceptin receptor genes (OPRK1 and OPRL1, respectively) and their endogenous ligands, preprodynorphin (PDYN) and prepronociceptin (PNOC), in the mesolimbic areas of rats with high and low voluntary alcohol consumption. Methods. Individually housed male Wistar rats were given a 25-day-long two-bottle (10% ethanol/water) free choice trial. mRNA levels were measured using the real-time polymerase chain reaction (qPCR). Results. Alcohol preferring rats progressively increased their ethanol consumption over the course of experiment while non-preferring, low-drinking animals controlled their alcohol intake near the baseline level. Alcohol non-preferring rats were identified to have significantly higher levels of PDYN and PNOC mRNA in the striatum and OPRK1 and OPRL1 mRNA in the amygdala compared to ethanol preferring animals. Conclusion. We suggested that higher levels of the “anti-reward opioid system” gene expression in mesolimbic structures may blunt the hedonic response to alcohol and thus preclude the increase in alcohol preference and uncontrolled excessive alcohol intake.

scholarly journals Acquired Ulcero-Mutilating Bilateral Acro-Osteopathy (Bureau-Barrière Syndrome)

2017 ◽  
Vol 5 (4) ◽  
pp. 558-560
Author(s):  
Georgi Tchernev ◽  
Hristo Mangarov ◽  
Ilia Lozev ◽  
Ivan Pidakev ◽  
Torello Lotti ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Lower Limb ◽  
Alcohol Intake ◽  
Clinical Presentation ◽  
Interdisciplinary Approach ◽  
Bone Lesions ◽  
Nail Dystrophy ◽  
Skin Changes ◽  
Excessive Alcohol ◽  
Excessive Alcohol Intake

We present a 35-year-old male patient with Bureau-Barrière syndrome. Bureau-Barrière syndrome is an ulcero-mutilating acropathy almost invariably associated with excessive alcohol intake. It presents with a triad of trophic skin changes with recurrent ulcerations, bone lesions and nerve damage. The clinical presentation includes chronic painless plantar ulcerations with periulcerous hyperkeratosis, hyperhidrosis, livedoid skin colour, nail dystrophy, widening and infiltration of the toes and common interdigital mycoses. Other non-specific skin changes related to the alcohol consumption are commonly observed as well. The condition affects mainly middle-aged men suffering from alcoholism. Often a bilateral location at the lower limb of male alcoholics has been described, as in our patient. Successful treatment of the Bureau-Barrière syndrome requires an interdisciplinary approach. Cessation of alcohol intake and smoking is of paramount importance.

scholarly journals Finding the Right Balance: A Social Norms Intervention to Reduce Heavy Drinking in University Students

2021 ◽  
Vol 9 ◽  
Author(s):  
Christine Wolter ◽  
Tino Lesener ◽  
Tobias Alexander Thomas ◽  
Alicia-Carolin Hentschel ◽  
Burkhard Gusy
Keyword(s):  
Alcohol Consumption ◽  
University Students ◽  
Social Norms ◽  
Alcohol Intake ◽  
Drinking Behavior ◽  
Intervention Group ◽  
Control Group ◽  
Alcohol Prevention ◽  
Normative Feedback ◽  
The Impact

Introduction: Heavy alcohol consumption constitutes a major health risk among University students. Social relationships with peers strongly affect University students' perception of the drinking behavior of others, which in turn plays a crucial role in determining their own alcohol intake. University students tend to overestimate their peers' alcohol consumption – a belief that is associated with an increase in an individual's own consumption. Therefore, we implemented a social norms intervention with personalized normative feedback at a major University in Germany to reduce and prevent excessive drinking among University students.Methods: Our intervention was part of a regular health monitoring survey. We invited all enrolled University students to take part in this survey on two occasions. A total of 862 University students completed the questionnaire, 563 (65.3%) of which received e-mail-based feedback upon request concerning their peers' and their own alcohol consumption. For the intervention group (n = 190) as well as the control group (no feedback requested; n = 101), we included only University students in the evaluation who overestimated their peers' alcohol use and indicated above average consumption of the peers. We applied analyses of variance to assess intervention effects with regard to the correction of overestimated group norms as well as University students' drinking behavior.Results: Within the intervention group, we observed a significantly larger reduction of the previously overestimated behavioral norms compared to the control group (p < 0.001; ηp2 = 0.06). With regard to behavioral outcomes the intervention group showed a significantly larger reduction in the AUDIT-C score (p = 0.020; ηp2 = 0.03).Discussion: Our study confirms previous research whereupon personalized, gender-specific and selective normative feedback is effective for alcohol prevention among University students. However, University students still overestimated their peers' alcohol intake after the intervention. Furthermore, we did not reach high-risk groups (University students with the highest alcohol intake) since no feedback was requested. Future studies should address factors influencing the impact of the intervention and reachability of selective groups.

scholarly journals Effects of a Peripherally Restricted Hybrid Inhibitor of CB1 Receptors and iNOS on Alcohol Drinking Behavior and Alcohol-Induced Endotoxemia

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5089
Author(s):  
Luis Santos-Molina ◽  
Alexa Herrerias ◽  
Charles N. Zawatsky ◽  
Ozge Gunduz-Cinar ◽  
Resat Cinar ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Intake ◽  
Dominant Role ◽  
Drinking Behavior ◽  
Endocannabinoid System ◽  
Cb1 Receptors ◽  
Relative Role ◽  
Inhibitory Function ◽  
Inos Inhibitor

Alcohol consumption is associated with gut dysbiosis, increased intestinal permeability, endotoxemia, and a cascade that leads to persistent systemic inflammation, alcoholic liver disease, and other ailments. Craving for alcohol and its consequences depends, among other things, on the endocannabinoid system. We have analyzed the relative role of central vs. peripheral cannabinoid CB1 receptors (CB1R) using a “two-bottle” as well as a “drinking in the dark” paradigm in mice. The globally acting CB1R antagonist rimonabant and the non-brain penetrant CB1R antagonist JD5037 inhibited voluntary alcohol intake upon systemic but not upon intracerebroventricular administration in doses that elicited anxiogenic-like behavior and blocked CB1R-induced hypothermia and catalepsy. The peripherally restricted hybrid CB1R antagonist/iNOS inhibitor S-MRI-1867 was also effective in reducing alcohol consumption after oral gavage, while its R enantiomer (CB1R inactive/iNOS inhibitor) was not. The two MRI-1867 enantiomers were equally effective in inhibiting an alcohol-induced increase in portal blood endotoxin concentration that was caused by increased gut permeability. We conclude that (i) activation of peripheral CB1R plays a dominant role in promoting alcohol intake and (ii) the iNOS inhibitory function of MRI-1867 helps in mitigating the alcohol-induced increase in endotoxemia.

scholarly journals A Smartphone App to Assess Alcohol Consumption Behavior: Development, Compliance, and Reactivity (Preprint)

2018 ◽  
Author(s):  
Antoinette Poulton ◽  
Jason Pan ◽  
Loren Richard Bruns Jr ◽  
Richard O Sinnott ◽  
Robert Hester
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Intake ◽  
Drinking Behavior ◽  
Experimental Period ◽  
Smartphone App ◽  
Healthy Population ◽  
Smartphone Apps ◽  
Group Status ◽  
Consumption Behavior ◽  
Study Protocols

BACKGROUND There are disadvantages—largely related to cost, participant burden, and missing data—associated with traditional electronic methods of assessing drinking behavior in real time. This potentially diminishes some of the advantages—namely, enhanced sample size and diversity—typically attributed to these methods. Download of smartphone apps to participants’ own phones might preserve these advantages. However, to date, few researchers have detailed the process involved in developing custom-built apps for use in the experimental arena or explored methodological concerns regarding compliance and reactivity. OBJECTIVE The aim of this study was to describe the process used to guide the development of a custom-built smartphone app designed to capture alcohol intake behavior in the healthy population. Methodological issues related to compliance with and reactivity to app study protocols were examined. Specifically, we sought to investigate whether hazard and nonhazard drinkers would be equally compliant. We also explored whether reactivity in the form of a decrease in drinking or reduced responding (“yes”) to drinking behavior would emerge as a function of hazard or nonhazard group status. METHODS An iterative development process that included elements typical of agile software design guided the creation of the CNLab-A app. Healthy individuals used the app to record alcohol consumption behavior each day for 21 days. Submissions were either event- or notification-contingent. We considered the size and diversity of the sample, and assessed the data for evidence of app protocol compliance and reactivity as a function of hazard and nonhazard drinker status. RESULTS CNLab-A yielded a large and diverse sample (N=671, mean age 23.12). On average, participants submitted data on 20.27 (SD 1.88) out of 21 days (96.5%, 20.27/21). Both hazard and nonhazard drinkers were highly compliant with app protocols. There were no differences between groups in terms of number of days of app use (P=.49) or average number of app responses (P=.54). Linear growth analyses revealed hazardous drinkers decreased their alcohol intake by 0.80 standard drinks over the 21-day experimental period. There was no change to the drinking of nonhazard individuals. Both hazard and nonhazard drinkers showed a slight decrease in responding (“yes”) to drinking behavior over the same period. CONCLUSIONS Smartphone apps participants download to their own phones are effective and methodologically sound means of obtaining alcohol consumption information for research purposes. Although further investigation is required, such apps might, in future, allow for a more thorough examination of the antecedents and consequences of drinking behavior.

scholarly journals Kappa Opioid Receptor and Dynorphin Signaling in the Central Amygdala Regulates Alcohol Intake

2019 ◽  
Author(s):  
Daniel W. Bloodgood ◽  
Dipanwita Pati ◽  
Melanie M. Pina ◽  
Sofia Neira ◽  
J. Andrew Hardaway ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Alcohol Drinking ◽  
Alcohol Intake ◽  
Gene Knockout ◽  
Kappa Opioid Receptor ◽  
Conditional Knockout ◽  
Central Nucleus ◽  
Kappa Opioid ◽  
Excessive Alcohol Consumption ◽  
Excessive Alcohol

AbstractExcessive alcohol drinking has been shown to modify brain circuitry to predispose individuals for future alcohol abuse. Previous studies have implicated the central nucleus of the amygdala (CeA) as an important site for mediating the somatic symptoms of withdrawal and for regulating alcohol intake. In addition, recent work has established a role for both the Kappa Opioid Receptor (KOR) and its endogenous ligand dynorphin in mediating these processes. However, it is unclear whether these effects are due to dynorphin or KOR arising from within the CeA itself or other input brain regions. To directly examine the role of preprodynorphin (PDYN) and KOR expression in CeA neurons, we performed region-specific conditional knockout of these genes and assessed the effects on the Drinking in the Dark (DID) and Intermittent Access (IA) paradigms. We then examined the effects of DID on PDYN and KOR modulation of CeA circuit physiology. Conditional gene knockout resulted in sex-specific responses wherein PDYN knockout decreased alcohol drinking in both male and female mice, whereas KOR knockout decreased drinking in males only. We also found that neither PDYN nor KOR knockout protected against anxiety caused by alcohol drinking. Lastly, a history of alcohol drinking did not alter synaptic transmission in PDYN neurons in the CeA of either sex, but excitability of PDYN neurons was increased in male mice only. Taken together, our findings indicate that PDYN and KOR signaling in the CeA plays an important role in regulating excessive alcohol consumption and highlight the need for future studies to examine how this is mediated through downstream effector regions.

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