scholarly journals Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants

2021 ◽  
Vol 12 ◽  
Author(s):  
Summer L. Thompson ◽  
Carol A. Gianessi ◽  
Stephanie S. O'Malley ◽  
Dana A. Cavallo ◽  
Julia M. Shi ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
Kinase Inhibitor ◽  
Human Study ◽  
Self Administration ◽  
Positive Effects ◽  
Fyn Kinase ◽  
Human Participants ◽  
Habitual Responding ◽  
Alcohol Seeking

More effective treatments to reduce pathological alcohol drinking are needed. The glutamatergic system and the NMDA receptor (NMDAR), in particular, are implicated in behavioral and molecular consequences of chronic alcohol use, making the NMDAR a promising target for novel pharmacotherapeutics. Ethanol exposure upregulates Fyn, a protein tyrosine kinase that indirectly modulates NMDAR signaling by phosphorylating the NR2B subunit. The Src/Fyn kinase inhibitor saracatinib (AZD0530) reduces ethanol self-administration and enhances extinction of goal-directed ethanol-seeking in mice. However, less is known regarding how saracatinib affects habitual ethanol-seeking. Moreover, no prior studies have assessed the effects of Src/Fyn kinase inhibitors on alcohol-seeking or consumption in human participants. Here, we tested the effects of saracatinib on alcohol consumption and craving/seeking in two species, including the first trial of an Src/Fyn kinase inhibitor to reduce drinking in humans. Eighteen male C57BL/6NCrl mice underwent operant conditioning on a variable interval schedule to induce habitual responding for 10% ethanol/0.1% saccharin. Next, mice received 5 mg/kg saracatinib or vehicle 2 h or 30 min prior to contingency degradation to measure habitual responding. In the human study, 50 non-treatment seeking human participants who drank heavily and met DSM-IV criteria for alcohol abuse or dependence were randomized to receive 125 mg/day saracatinib (n = 33) or placebo (n = 17). Alcohol Drinking Paradigms (ADP) were completed in a controlled research setting: before and after 7–8 days of treatment. Each ADP involved consumption of a priming drink of alcohol (0.03 mg%) followed by ad libitum access (3 h) to 12 additional drinks (0.015 g%); the number of drinks consumed and craving (Alcohol Urge Questionnaire) were recorded. In mice, saracatinib did not affect habitual ethanol seeking or consumption at either time point. In human participants, no significant effects of saracatinib on alcohol craving or consumption were identified. These results in mice and humans suggest that Fyn kinase inhibition using saracatinib, at the doses tested here, may not reduce alcohol consumption or craving/seeking among those habitually consuming alcohol, in contrast to reports of positive effects of saracatinib in individuals that seek ethanol in a goal-directed manner. Nevertheless, future studies should confirm these negative findings using additional doses and schedules of saracatinib administration.

Effect of the Covid-19 Italian lockdown on human health: the analysis of alcohol consumption for aware quarantine (Preprint)

2020 ◽  
Author(s):  
Chiara Mazzarella ◽  
Annamaria Spina ◽  
Marcello Dallio ◽  
Antonietta Gerarda Gravina ◽  
Mario Romeo ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Abuse ◽  
Psychosocial Factors ◽  
Alcohol Drinking ◽  
Psychosocial Support ◽  
Human Life ◽  
Stressful Event ◽  
Drinking Behaviour ◽  
Drinking Habits ◽  
Specific Subset

BACKGROUND Italy has been one of the first western countries seriously involved in the COVID-19 pandemic in the first months of 2020 and so that the national government was forced to impose a long lockdown period, stopping all the people aggregation outdoor and indoor activities. From a social point of view this period of domestic confinement resulted in deep changes of behaviours and lifestyles, promoting in many people the onset of psychological symptoms and signs (including anxiety, depression, insomnia, and irritability among others) already known as associated with drug and alcohol abuse OBJECTIVE this study aims to assess the variation of alcohol drinking habits in a sample of Italian citizens during the COVID-19 lockdown and to identify the psychosocial factors surrounding it, in order to assess the specific subset of the population that could need psychosocial support during these events METHODS An online anonymous questionnaire was created and submitted from 9th April 2020 to 28th April 2020 using social medias and e-mails. Questions were related to personal details such as age, work, instruction, and, moreover, to alcohol drinking habits during the lockdown, including Alcohol Use Disorders Identification Test (AUDIT C) test questions RESULTS A total of 1234 surveys were filled out by subjects with an age range from 18 to 80 years old. An increase in both anxiety and fear has been detected in most of the participants (63% and 61% respectively) with a direct (r=0.652; p<0.001) relationship between them. Participants older than 50 years showed the strongest correlation between alcohol consumption, fear, and anxiety, (r=0.830, P <0.001 and r=0.741, P<0.001, respectively). Subjects living alone experienced a stronger association between anxiety, fear, and higher level of alcohol consumption (r: 0.529; P<0.001; r: 0.628, P<0.001 respectively). Moreover, 18% of participants increased alcohol consumption drinking during the lockdown. These subjects showed a lower frequency of alcohol consumption before the lockdown in comparison to the rest of the study population (2.5±0.96 vs 3±1.03, P<0.0001 respectively). Moreover, comparing the abovementioned groups, the percentage of subjects who experienced higher alcohol assumption before the 11th of March was higher in those that didn't change their drinking behaviour during the lockdown in comparison to that portion of them that experienced a worsening of alcohol abuse (r: 30.422, P<0.0001) CONCLUSIONS according to these data, during the Italian lockdown due to COVID 19 pandemic, different kind of people experienced an increase in alcohol drinking. Several psychosocial factors are involved in determining the increase in harmful alcohol consumption during this extraordinary stressful event and they must be addressed by the healthcare support in order to avoid awful lockdown impact on human life

Effects of Stress on Alcohol Consumption in Rats Selectively Bred for High or Low Alcohol Drinking

2004 ◽  
Vol 28 (3) ◽  
pp. 385-393 ◽  
Author(s):  
Julia A. Chester ◽  
Annette M. Blose ◽  
Mark Zweifel ◽  
Janice C. Froehlich
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
Effects Of Stress ◽  
Low Alcohol

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 Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation study

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e026860 ◽  
Author(s):  
Luqi Shen ◽  
José F Cordero ◽  
Jia-Sheng Wang ◽  
Ye Shen ◽  
Shengxu Li ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
Blood Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Risk Scores ◽  
Mendelian Randomisation ◽  
Lipid Levels ◽  
Genetically Determined

ObjectivesThe objective of this study was to evaluate the association of genetically determined leptin with lipids.DesignWe conducted a Mendelian randomisation study to assess a potential causal relationship between serum leptin and lipid levels. We also evaluated whether alcohol drinking modified the associations of genetically determined leptin with blood lipids.Setting and participants3860 participants of the Framingham Heart Study third generation cohort.ResultsBoth genetic risk scores (GRSs), the GRS generated using leptin loci independent of body mass index (BMI) and GRS generated using leptin loci dependent of BMI, were positively associated with log-transformed leptin (log-leptin). The BMI-independent leptin GRS was associated with log-transformed triglycerides (log-TG, β=−0.66, p=0.01), but not low-density lipoprotein cholesterol (LDL-C, p=0.99), high-density lipoprotein cholesterol (HDL-C, p=0.44) or total cholesterol (TC, p=0.49). Instrumental variable estimation showed that per unit increase in genetically determined log-leptin was associated with 0.55 (95% CI: 0.05 to 1.00) units decrease in log-TG. Besides significant association with log-TG (β=−0.59, p=0.009), the BMI-dependent GRS was nominally associated with HDL-C (β=−10.67, p=0.09) and TC (β=−28.05, p=0.08). When stratified by drinking status, the BMI-dependent GRS was associated with reduced levels of LDL-C (p=0.03), log-TG (p=0.004) and TC (p=0.003) among non-current drinkers only. Significant interactions between the BMI-dependent GRS and alcohol drinking were identified for LDL-C (p=0.03), log-TG (p=0.03) and TC (p=0.02).ConclusionThese findings together indicated that genetically determined leptin was negatively associated with lipid levels and the association may be modified by alcohol consumption.

scholarly journals Relevance of the body mass index in the cognitive status of diabetic patients with different alcohol-drinking patterns

2014 ◽  
Vol 66 (1) ◽  
pp. 347-353
Author(s):  
Serban Lacramioara ◽  
Cristina Toarba ◽  
Simona Hogas ◽  
A. Covic ◽  
A. Ciobica ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
The Body ◽  
Control Group ◽  
Diabetic Patients ◽  
Inverse Association ◽  
Drinking Patterns ◽  
Alcohol Drinking Patterns ◽  
The Relationship

Nowadays the general relevance of alcohol consumption in diabetes is extremely controversial. There are recent reports that alcohol consumption could result in a decreased incidence of diabetes, as well as other studies demonstrating a positive association between alcohol consumption and type 2 diabetes; there are also reports arguing for an inverse association between the two or for no correlation at all. The different results obtained in these studies could be explained by the existence of several confounders that could influence the outcome of the aforementioned studies. In this paper, we studied the possible relevance of BMI as a confounder in the relationship between alcohol consumption in diabetes and cognitive function, by analyzing the correlations between BMI values in diabetic patients with different alcohol drinking patterns and the subdomains from some main psychometric tests, such as MMSE (Mini-Mental State Examination) and MOCA (Montreal Cognitive Assessment). Our results provide evidence for BMI as a possible confounder of the relationship between alcohol consumption in diabetes and cognitive function. We found a significant increase (p<0.0001) in BMI values in patients with diabetes compared to our control group. Most importantly, significant correlations between BMI parameters in alcohol-consuming diabetic patients and most of the subdomains for psychometric testing.

scholarly journals Effectiveness of Digital Interventions for Reducing Behavioral Risks of Cardiovascular Disease in Nonclinical Adult Populations: Systematic Review of Reviews

10.2196/19688 ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. e19688
Author(s):  
Natalie Gold ◽  
Amy Yau ◽  
Benjamin Rigby ◽  
Chris Dyke ◽  
Elizabeth Alice Remfry ◽  
...  
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Alcohol Consumption ◽  
Meta Analysis ◽  
Face To Face ◽  
Positive Effects ◽  
Digital Interventions ◽  
Diet And Physical Activity ◽  
Intent To Treat

Background Digital health interventions are increasingly being used as a supplement or replacement for face-to-face services as a part of predictive prevention. They may be offered to those who are at high risk of cardiovascular disease and need to improve their diet, increase physical activity, stop smoking, or reduce alcohol consumption. Despite the popularity of these interventions, there is no overall summary and comparison of the effectiveness of different modes of delivery of a digital intervention to inform policy. Objective This review aims to summarize the effectiveness of digital interventions in improving behavioral and health outcomes related to physical activity, smoking, alcohol consumption, or diet in nonclinical adult populations and to identify the effectiveness of different modes of delivery of digital interventions. Methods We reviewed articles published in the English language between January 1, 2009, and February 25, 2019, that presented a systematic review with a narrative synthesis or meta-analysis of any study design examining digital intervention effectiveness; data related to adults (≥18 years) in high-income countries; and data on behavioral or health outcomes related to diet, physical activity, smoking, or alcohol, alone or in any combination. Any time frame or comparator was considered eligible. We searched MEDLINE, Embase, PsycINFO, Cochrane Reviews, and gray literature. The AMSTAR-2 tool was used to assess review confidence ratings. Results We found 92 reviews from the academic literature (47 with meta-analyses) and 2 gray literature items (1 with a meta-analysis). Digital interventions were typically more effective than no intervention, but the effect sizes were small. Evidence on the effectiveness of digital interventions compared with face-to-face interventions was mixed. Most trials reported that intent-to-treat analysis and attrition rates were often high. Studies with long follow-up periods were scarce. However, we found that digital interventions may be effective for up to 6 months after the end of the intervention but that the effects dissipated by 12 months. There were small positive effects of digital interventions on smoking cessation and alcohol reduction; possible effectiveness in combined diet and physical activity interventions; no effectiveness for interventions targeting physical activity alone, except for when interventions were delivered by mobile phone, which had medium-sized effects; and no effectiveness observed for interventions targeting diet alone. Mobile interventions were particularly effective. Internet-based interventions were generally effective. Conclusions Digital interventions have small positive effects on smoking, alcohol consumption, and in interventions that target a combination of diet and physical activity. Small effects may have been due to the low efficacy of treatment or due to nonadherence. In addition, our ability to make inferences from the literature we reviewed was limited as those interventions were heterogeneous, many reviews had critically low AMSTAR-2 ratings, analysis was typically intent-to-treat, and follow-up times were relatively short. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42019126074; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=126074.

scholarly journals Stress vulnerability promotes an alcohol prone phenotype in a preclinical model of sustained depression

2018 ◽  
Author(s):  
Danai Riga ◽  
Leanne JM Schmitz ◽  
Yvar van Mourik ◽  
Witte JG Hoogendijk ◽  
Taco J De Vries ◽  
...  
Keyword(s):  
Social Defeat ◽  
Preclinical Model ◽  
Self Administration ◽  
Depression Vulnerability ◽  
Stress Vulnerability ◽  
The Social ◽  
Depression Proneness ◽  
Male Wistar Rats ◽  
Alcohol Seeking

AbstractMajor depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (5 episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction and cue-induced reinstatement of alcohol-seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, excessive motivation to acquire alcohol, persistent alcohol-seeking despite alcohol unavailability, extinction resistance and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol-seeking and -taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.

COVID-19 and Alcohol Misuse: A Case Report

2021 ◽  
Vol 21 ◽  
Author(s):  
Ali Asadollahi-Amin ◽  
Ali Nowroozi ◽  
Mehrdad Hasibi ◽  
Behzad Asanjarani ◽  
SeyedAhmad SeyedAlinaghi
Keyword(s):  
Social Media ◽  
Case Report ◽  
Immune System ◽  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
Alcohol Misuse ◽  
The Body ◽  
False Information ◽  
In The Beginning

Abstract: In the beginning of 2020, a newly emerged virus, now named SARS-CoV-2, began to spread in China. After four months, it has reached all over the globe, infecting more than 2.5 million people. Currently, there are no proved treatments available. However, in social media, false information about alcohol consumption and its role against the virus is spreading. We described a victim of these false facts who presented with reduced eyesight due to alcohol drinking, a few days later showed symptoms of COVID-19 and, even though treated, lost his eyesight partially. Alcohol taking has no preventive or curing effect on COVID-19 and negatively impacts the body and immune system, which, therefore, should not be considered a treatment for COVID-19 disease.

Alcohol Consumption, Transgression, and Death

Dying to Eat ◽  
2018 ◽  
Author(s):  
Christa Shusko
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
Male Bonding ◽  
Baptist Identity

Christa Shusko’s chapter focuses on how alcohol-drinking rituals mimic the drinking of blood (really a “blood” punch) in male fraternity groups. Shusko’s chapter examines how the living face death and form community through food, albeit through male bonding rituals of consuming alcohol and reenacting illicit and horrific acts. Shusko contends that alcohol acts as both conduit and medium through which the living come to terms with both death and the macabre. Unlike Graham, who argues that the absence of alcohol reinforces Protestant, and particularly Baptist identity, Shusko points to the use of alcohol as a cohesive agent that brings the community together.

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