Exposure to alcohol advertising and alcohol consumption among Australian adolescents.

PubMed

Jones, Sandra C; Magee, Christopher A

2011-01-01

Underage drinking is a major problem in Australia and may be influenced by exposure to alcohol advertising. The objective of the present study was to collect data on 12-17 year old Australian adolescents' exposure to different types of alcohol advertising and examine the association between exposure to advertising and alcohol consumption. A cross-sectional survey of 1113 adolescents aged 12-17 years recruited with a variety of methods to gain a cross-section of participants across metropolitan, regional and rural New South Wales (including independent schools, mall intercepts and online). Participants answered a series of questions assessing adolescents' exposure to alcohol advertising across eight media (including television, Internet and point-of-sale). Alcohol consumption was assessed using three questions (initiation, recent consumption and frequency of consumption in the previous 12 months). The majority indicated that they had been exposed to alcohol advertisements on television, in newspapers and magazines, on the Internet, on billboards/posters and promotional materials and in bottleshops, bars and pubs; exposure to some of these types of alcohol advertisements was associated with increased alcohol consumption, with differences by age and gender. The results are consistent with studies from other countries and suggest that exposure to alcohol advertisements among Australian adolescents is strongly associated with drinking patterns. Given current high levels of drinking among Australian youth, these findings suggest the need to address the high levels of young people's exposure to alcohol advertising.

Neuroimmune Function and the Consequences of Alcohol Exposure

PubMed Central

Crews, Fulton T.; Sarkar, Dipak K.; Qin, Liya; Zou, Jian; Boyadjieva, Nadka; Vetreno, Ryan P.

2015-01-01

Induction of neuroimmune genes by binge drinking increases neuronal excitability and oxidative stress, contributing to the neurobiology of alcohol dependence and causing neurodegeneration. Ethanol exposure activates signaling pathways featuring high-mobility group box 1 and Toll-like receptor 4 (TLR4), resulting in induction of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells, which regulates expression of several cytokine genes involved in innate immunity, and its target genes. This leads to persistent neuroimmune responses to ethanol that stimulate TLRs and/or certain glutamate receptors (i.e., N-methyl-d-aspartate receptors). Alcohol also alters stress responses, causing elevation of peripheral cytokines, which further sensitize neuroimmune responses to ethanol. Neuroimmune signaling and glutamate excitotoxicity are linked to alcoholic neurodegeneration. Models of alcohol abuse have identified significant frontal cortical degeneration and loss of hippocampal neurogenesis, consistent with neuroimmune activation pathology contributing to these alcohol-induced, long-lasting changes in the brain. These alcohol-induced long-lasting increases in brain neuroimmune-gene expression also may contribute to the neurobiology of alcohol use disorder. PMID:26695754

Gender and Impulsivity: Effects on Cue-Induced Alcohol Craving.

PubMed

Yarmush, Devorah E; Manchery, Linda; Luehring-Jones, Peter; Erblich, Joel

2016-05-01

Numerous studies have demonstrated that trait impulsivity is linked to increased risk of developing alcohol-use disorders and other substance abuse. Impulsivity has also been shown in some studies to potentiate cue-induced drug cravings. Despite considerable evidence of gender differences in impulsivity and drug craving among individuals suffering from alcohol dependence and other drug use, little research has focused on these processes in healthy young men and women who may be at risk for developing alcohol-use disorders. The objective of this study was to investigate the relationship between impulsivity and cue-induced craving, as well as possible gender differences in these effects among healthy young adults. To that end, female (n = 22) and male (n = 14) social drinkers aged 18 to 25, recruited from an urban university campus, completed the Barratt Impulsiveness Scale and reported their alcohol cravings immediately before and after laboratory exposure to alcohol cues. Findings indicated that exposure to cues elicited increased alcohol cravings, but these effects did not differ by gender. Interestingly, a significant interaction of impulsivity and gender revealed that impulsivity predicted significantly higher cue-induced cravings in women, but not men. Findings underscore the importance of better understanding the interaction of situational factors (e.g., exposure to alcohol cues) and dispositional factors (e.g., impulsivity) as potential contributors to drinking motivation. Future prospective research is needed to identify gender-specific risk factors for the development of problem drinking. Copyright © 2016 by the Research Society on Alcoholism.

5-Mehtyltetrahydrofolate rescues alcohol-induced neural crest cell migration abnormalities.

PubMed

Shi, Yu; Li, Jiejing; Chen, Chunjiang; Gong, Manzi; Chen, Yuan; Liu, Youxue; Chen, Jie; Li, Tingyu; Song, Weihong

2014-09-16

Alcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis. Pre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4% ± 4.4%, total embryo n = 234), and 1.5% and 2.0% dramatically augment the deformation to 81.2% ± 6.5% (n = 205) and 91.6% ± 3.0% (n = 235), respectively (P < 0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies. Our study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.

Effects of methylmercury and alcohol exposure in Drosophila melanogaster: Potential risks in neurodevelopmental disorders.

PubMed

Chauhan, Ved; Chauhan, Abha

2016-06-01

Extensive evidence suggests the role of oxidative stress in autism and other neurodevelopmental disorders. In this study, we investigated whether methylmercury (MeHg) and/or alcohol exposure has deleterious effects in Drosophila melanogaster (fruit flies). A diet containing different concentrations of MeHg in Drosophila induced free radical generation and increased lipid peroxidation (markers of oxidative stress) in a dose-dependent manner. This effect of MeHg on oxidative stress was enhanced by further exposure to alcohol. It was observed that alcohol alone could also induce free radical generation in flies. After alcohol exposure, MeHg did not affect the immobilization of flies, but it increased the recovery time in a concentration-dependent manner. MeHg significantly inhibited the activity of alcohol dehydrogenase (ADH) in a dose-dependent manner. Linear regression analysis showed a significant negative correlation between ADH activity and recovery time upon alcohol exposure in the flies fed a diet with MeHg. This relationship between ADH activity and recovery time after alcohol exposure was confirmed by adding 4-methyl pyrazole (an inhibitor of ADH) to the diet for the flies. These results suggest that consumption of alcohol by pregnant mothers who are exposed to MeHg may lead to increased oxidative stress and to increased length of time for alcohol clearance, which may have a direct impact on the development of the fetus, thereby increasing the risk of neurodevelopmental disorders. Published by Elsevier Ltd.

Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity

PubMed Central

Guidolin, Valeria; Balbo, Silvia

2018-01-01

Alcohol is classified by the International Agency for Research on Cancer (IARC) as a human carcinogen and its consumption has been associated to an increased risk of liver, breast, colorectum, and upper aerodigestive tract (UADT) cancers. Its mechanisms of carcinogenicity remain unclear and various hypotheses have been formulated depending on the target organ considered. In the case of UADT cancers, alcohol’s major metabolite acetaldehyde seems to play a crucial role. Acetaldehyde reacts with DNA inducing modifications, which, if not repaired, can result in mutations and lead to cancer development. Despite alcohol being mainly metabolized in the liver, several studies performed in humans found higher levels of acetaldehyde in saliva compared to those found in blood immediately after alcohol consumption. These results suggest that alcohol-derived acetaldehyde exposure may occur in the oral cavity independently from liver metabolism. This hypothesis is supported by our recent results showing the presence of acetaldehyde-related DNA modifications in oral cells of monkeys and humans exposed to alcohol, overall suggesting that the alcohol metabolism in the oral cavity is an independent cancer risk factor. This review article will focus on illustrating the factors modulating alcohol-derived acetaldehyde exposure and effects in the oral cavity. PMID:29342885

Adolescent Alcohol Exposure: Burden of Epigenetic Reprogramming, Synaptic Remodeling, and Adult Psychopathology

PubMed Central

Kyzar, Evan J.; Floreani, Christina; Teppen, Tara L.; Pandey, Subhash C.

2016-01-01

Adolescence represents a crucial phase of synaptic maturation characterized by molecular changes in the developing brain that shape normal behavioral patterns. Epigenetic mechanisms play an important role in these neuromaturation processes. Perturbations of normal epigenetic programming during adolescence by ethanol can disrupt these molecular events, leading to synaptic remodeling and abnormal adult behaviors. Repeated exposure to binge levels of alcohol increases the risk for alcohol use disorder (AUD) and comorbid psychopathology including anxiety in adulthood. Recent studies in the field clearly suggest that adolescent alcohol exposure causes widespread and persistent changes in epigenetic, neurotrophic, and neuroimmune pathways in the brain. These changes are manifested by altered synaptic remodeling and neurogenesis in key brain regions leading to adult psychopathology such as anxiety and alcoholism. This review details the molecular mechanisms underlying adolescent alcohol exposure-induced changes in synaptic plasticity and the development of alcohol addiction-related phenotypes in adulthood. PMID:27303256

Alcohol-Induced Histone Acetylation Reveals a Gene Network Involved in Alcohol Tolerance

PubMed Central

Ghezzi, Alfredo; Krishnan, Harish R.; Lew, Linda; Prado, Francisco J.; Ong, Darryl S.; Atkinson, Nigel S.

2013-01-01

Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol. PMID:24348266

Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug dependence.

PubMed

Yates, W R; Cadoret, R J; Troughton, E P; Stewart, M; Giunta, T S

1998-06-01

The objective of this study is to examine the effect of fetal alcohol exposure on later substance dependence using an adoption study method. One hundred ninety-seven adoptees were interviewed for substance abuse disorders, including nicotine, alcohol, and drug dependence. Twenty-one adoptees had mothers who drank during pregnancy. Adoptees with fetal alcohol exposure were compared with those without fetal alcohol exposure for symptoms of adult nicotine, alcohol, and drug dependence. Adoptee symptom counts for alcohol, drug, and nicotine dependence were higher for those exposed to alcohol in utero. The effect of fetal alcohol exposure remained after controlling for gender, biological parent alcohol dependence diagnosis, birth weight, gestational age and other environmental variables. Fetal alcohol exposure may produce increased risk for later nicotine, alcohol, and drug dependence. Possible effects of fetal alcohol exposure on development of adult substance use patterns needs attention in genetic studies of substance abuse.

Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits

PubMed Central

Bonthius, Daniel J.; Winters, Zachary; Karacay, Bahri; Bousquet, Samantha Larimer; Bonthius, Daniel J.

2014-01-01

The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS−/− mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS−/− mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS−/− mice and their wild type controls received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days 4–9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS−/− and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS−/− mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS−/− mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS−/− mice, but not

European longitudinal study on the relationship between adolescents' alcohol marketing exposure and alcohol use.

PubMed

de Bruijn, Avalon; Tanghe, Jacqueline; de Leeuw, Rebecca; Engels, Rutger; Anderson, Peter; Beccaria, Franca; Bujalski, Michał; Celata, Corrado; Gosselt, Jordy; Schreckenberg, Dirk; Słodownik, Luiza; Wothge, Jördis; van Dalen, Wim

2016-10-01

This is the first study to examine the effect of alcohol marketing exposure on adolescents' drinking in a cross-national context. The aim was to examine reciprocal processes between exposure to a wide range of alcohol marketing types and adolescent drinking, controlled for non-alcohol branded media exposure. Prospective observational study (11-12- and 14-17-month intervals), using a three-wave autoregressive cross-lagged model. School-based sample in 181 state-funded schools in Germany, Italy, Netherlands, Poland. A total of 9075 eligible respondents participated in the survey (mean age 14 years, 49.5% male. Adolescents reported their frequency of past-month drinking and binge drinking. Alcohol marketing exposure was measured by a latent variable with 13 items measuring exposure to online alcohol marketing, televised alcohol advertising, alcohol sport sponsorship, music event/festival sponsorship, ownership alcohol-branded promotional items, reception of free samples and exposure to price offers. Confounders were age, gender, education, country, internet use, exposure to non-alcohol sponsored football championships and television programmes without alcohol commercials. The analyses showed one-directional long-term effects of alcohol marketing exposure on drinking (exposure T1 on drinking T2: β = 0.420 (0.058), P < 0.001, 95% confidence interval (CI) = 0.324-0.515; exposure T2 on drinking T3: β = 0.200 (0.044), P < 0.001, 95% CI = 0.127-0.272; drinking T1 and drinking T2 on exposure: P > 0.05). Similar results were found in the binge drinking model (exposure T1 on binge T2: β = 0.409 (0.054), P < 0.001, 95% CI = 0.320-0.499; exposure T2 on binge T3: β = 0.168 (0.050), P = 0.001, 95% CI = 0.086-0.250; binge T1 and binge T2 on exposure: P > 0.05). There appears to be a one-way effect of alcohol marketing exposure on adolescents' alcohol use over time, which cannot be explained by either previous drinking or

Exposure to televised alcohol ads and subsequent adolescent alcohol use.

PubMed

Stacy, Alan W; Zogg, Jennifer B; Unger, Jennifer B; Dent, Clyde W

2004-01-01

To assess the impact of televised alcohol commercials on adolescents' alcohol use. Adolescents completed questionnaires about alcohol commercials and alcohol use in a prospective study. A one standard deviation increase in viewing television programs containing alcohol commercials in seventh grade was associated with an excess risk of beer use (44%), wine/liquor use (34%), and 3-drink episodes (26%) in eighth grade. The strength of associations varied across exposure measures and was most consistent for beer. Although replication is warranted, results showed that exposure was associated with an increased risk of subsequent beer consumption and possibly other consumption variables.

Zinc Deprivation Mediates Alcohol-Induced Hepatocyte IL-8 Analog Expression in Rodents via an Epigenetic Mechanism

PubMed Central

Zhao, Yantao; Zhong, Wei; Sun, Xiuhua; Song, Zhenyuan; Clemens, Dahn L.; Kang, Y. James; McClain, Craig J.; Zhou, Zhanxiang

2011-01-01

Neutrophil infiltration caused by IL-8 production is a central mechanism in alcohol-induced hepatitis. This study was performed to examine if an epigenetic mechanism is involved in alcohol-induced IL-8 production. Mice were pair-fed an alcohol-containing liquid diet for 4 weeks. Alcohol exposure induced hepatitis as indicated by increased expression of keratinocyte-derived cytokine (mouse IL-8) and neutrophil infiltration. Alcohol exposure induced histone 3 hyperacetylation owing to inhibition of histone deacetylase (HDAC) in association with NF-κB activation. Cell culture studies showed that alcohol exposure induced IL-8 and cytokine-induced neutrophil chemoattractant-1 (CINC-1, rat IL-8) production in human VL-17A cells and rat H4IIEC3 cells, respectively, dependent on acetaldehyde production, oxidative stress, and zinc release. Zinc deprivation alone induced CINC-1 production and acted synergistically with lipopolysaccharide or tumor necrosis factor-α on CINC-1 production. Zinc deprivation induced histone 3 hyperacetylation at lysine 9 through suppression of HDAC activity. Zinc deprivation caused nuclear translocation of NF-κB, and reduced HDAC binding to NF-κB. Chromatin immunoprecipitation (ChIP) showed that zinc deprivation caused histone 3 hyperacetylation as well as increased NF-κB binding to the CINC-1 promoter. In conclusion, inactivation of HDAC caused by zinc deprivation is a novel mechanism underlying IL-8 up-regulation in alcoholic hepatitis. PMID:21708112

Effects of Chronic Alcohol Exposure on the Modulation of Ischemia-Induced Glutamate Release via Cannabinoid Receptors in the Dorsal Hippocampus.

PubMed

Zheng, Lei; Wu, Xiaoda; Dong, Xiao; Ding, Xinli; Song, Cunfeng

2015-10-01

Chronic alcohol consumption is a critical contributing factor to ischemic stroke, as it enhances ischemia-induced glutamate release, leading to more severe excitotoxicity and brain damage. But the neural mechanisms underlying this phenomenon are poorly understood. We evaluated the effects of chronic alcohol exposure on the modulation of ischemia-induced glutamate release via CB1 and CB2 cannabinoid receptors during middle cerebral artery occlusion, using in vivo microdialysis coupled with high-performance liquid chromatography, in alcohol-naïve rats or rats after 1 or 30 days of withdrawal from chronic ethanol intake (6% v/v for 14 days). Intra-dorsal hippocampus (DH) infusions of ACEA or JWH133, selective CB1 or CB2 receptor agonists, respectively, decreased glutamate release in the DH in alcohol-naïve rats in a dose-dependent manner. Such an effect was reversed by co-infusions of SR141716A or AM630, selective CB1 or CB2 receptor antagonists, respectively. After 30 days, but not 1 day of withdrawal, ischemia induced an enhancement in glutamate release in the DH, as compared with non-alcohol-treated control group. Intra-DH infusions of JWH133, but not ACEA, inhibited ischemia-induced glutamate release in the DH after 30 days of withdrawal. Finally, 1 day of withdrawal did not alter the protein level of CB1 or CB2 receptors in the DH, as compared to non-alcohol-treated control rats. Whereas 30 days of withdrawal robustly decreased the protein level of CB1 receptors, but failed to alter the protein level of CB2 receptors, in the DH, as compared to non-alcohol-treated control rats. Together, these findings suggest that loss of expression/function of CB1 receptors, but not CB2 receptors in the DH, is correlated with the enhancement of ischemia-induced glutamate release after prolonged alcohol withdrawal. Copyright © 2015 by the Research Society on Alcoholism.

Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.

PubMed

Sun, Qian; Zhang, Wenliang; Zhong, Wei; Sun, Xinguo; Zhou, Zhanxiang

2016-10-01

Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP. This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD. Copyright © 2016 by the Research Society on Alcoholism.

Zinc deprivation mediates alcohol-induced hepatocyte IL-8 analog expression in rodents via an epigenetic mechanism.

PubMed

Zhao, Yantao; Zhong, Wei; Sun, Xiuhua; Song, Zhenyuan; Clemens, Dahn L; Kang, Y James; McClain, Craig J; Zhou, Zhanxiang

2011-08-01

Neutrophil infiltration caused by IL-8 production is a central mechanism in alcohol-induced hepatitis. This study was performed to examine if an epigenetic mechanism is involved in alcohol-induced IL-8 production. Mice were pair-fed an alcohol-containing liquid diet for 4 weeks. Alcohol exposure induced hepatitis as indicated by increased expression of keratinocyte-derived cytokine (mouse IL-8) and neutrophil infiltration. Alcohol exposure induced histone 3 hyperacetylation owing to inhibition of histone deacetylase (HDAC) in association with NF-κB activation. Cell culture studies showed that alcohol exposure induced IL-8 and cytokine-induced neutrophil chemoattractant-1 (CINC-1, rat IL-8) production in human VL-17A cells and rat H4IIEC3 cells, respectively, dependent on acetaldehyde production, oxidative stress, and zinc release. Zinc deprivation alone induced CINC-1 production and acted synergistically with lipopolysaccharide or tumor necrosis factor-α on CINC-1 production. Zinc deprivation induced histone 3 hyperacetylation at lysine 9 through suppression of HDAC activity. Zinc deprivation caused nuclear translocation of NF-κB, and reduced HDAC binding to NF-κB. Chromatin immunoprecipitation (ChIP) showed that zinc deprivation caused histone 3 hyperacetylation as well as increased NF-κB binding to the CINC-1 promoter. In conclusion, inactivation of HDAC caused by zinc deprivation is a novel mechanism underlying IL-8 up-regulation in alcoholic hepatitis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

PubMed

Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

2016-07-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. Copyright © 2016 by

Dietary fisetin supplementation protects against alcohol-induced liver injury in mice

PubMed Central

Sun, Qian; Zhang, Wenliang; Zhong, Wei; Sun, Xinguo; Zhou, Zhanxiang

2016-01-01

Background Overproduction of reactive oxygen species (ROS) is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary inverventions for multiple diseases including ALD. The objective of the present study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. Methods C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol diet for four weeks with or without fisetin supplementation at 10 mg/kg/d. Results Alcohol feeding induced lipid accumulation in the liver and increased plasma ALT and AST activities, which were attenuated by fisetin suplementation. The ethanol concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin suplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin suplementation remarkably reduced hepatic NADPH oxidase 4 (NOX4) levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal (4HNE) levels after alcohol exposure. Alcohol-induced apoptosis and upregulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin suplementation attenuated alcohol-induced hepatic streatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP. Conclusion The present study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating ethanol clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD. PMID:27575873

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

PubMed Central

Lunde, Emilie R.; Washburn, Shannon E.; Golding, Michael C.; Bake, Shameena; Miranda, Rajesh C.; Ramadoss, Jayanth

2016-01-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466

Assessment of the cerebellar neurotoxic effects of nicotine in prenatal alcohol exposure in rats.

PubMed

Bhattacharya, Dwipayan; Majrashi, Mohammed; Ramesh, Sindhu; Govindarajulu, Manoj; Bloemer, Jenna; Fujihashi, Ayaka; Crump, Bailee-Ryan; Hightower, Harrison; Bhattacharya, Subhrajit; Moore, Timothy; Suppiramaniam, Vishnu; Dhanasekaran, Muralikrishnan

2018-02-01

The adverse effects of prenatal nicotine and alcohol exposure on human reproductive outcomes are a major scientific and public health concern. In the United States, substantial percentage of women (20-25%) of childbearing age currently smoke cigarettes and consume alcohol, and only a small percentage of these individuals quit after learning of their pregnancy. However, there are very few scientific reports on the effect of nicotine in prenatal alcohol exposure on the cerebellum of the offspring. Therefore, this study was conducted to investigate the cerebellar neurotoxic effects of nicotine in a rodent model of Fetal Alcohol Spectrum Disorder (FASD). In this study, we evaluated the behavioral changes, biochemical markers of oxidative stress and apoptosis, mitochondrial functions and the molecular mechanisms associated with nicotine in prenatal alcohol exposure on the cerebellum. Prenatal nicotine and alcohol exposure induced oxidative stress, did not affect the mitochondrial functions, increased the monoamine oxidase activity, increased caspase expression and decreased ILK, PSD-95 and GLUR1 expression without affecting the GSK-3β. Thus, our current study of prenatal alcohol and nicotine exposure on cerebellar neurotoxicity may lead to new scientific perceptions and novel and suitable therapeutic actions in the future. Copyright © 2017. Published by Elsevier Inc.

Playfulness and prenatal alcohol exposure: a comparative study.

PubMed

Pearton, Jordan Louise; Ramugondo, Elelwani; Cloete, Lizahn; Cordier, Reinie

2014-08-01

South Africa carries a high burden of alcohol abuse. The effects of maternal alcohol consumption during pregnancy are most pronounced in poor, rural communities. Earlier research suggests that children with prenatal alcohol exposure have poor social behaviour; however, to date, no research has investigated their playfulness. This study investigated the differences in playfulness of children with and without prenatal alcohol exposure. Grade one learners with a positive history of prenatal alcohol exposure (n = 15) and a reference group without a positive history of prenatal alcohol exposure (n = 15) were filmed engaging in free play at their schools. The Test of Playfulness was used to measure playfulness from recordings. Data were subjected to Rasch analysis to calculate interval level measure scores for each participant. The overall measure scores and individual Test of Playfulness social items were subjected to paired samples t-tests to calculate if significant differences existed between the groups. Children with prenatal alcohol exposure had a significantly lower mean overall playfulness score than the reference group (t = -2.51; d.f. = 28; P = 0.02). Children with prenatal alcohol exposure also scored significantly lower than the reference group on 5 of the 12 Test of Playfulness items related to social play. This research suggests that children with prenatal alcohol exposure are more likely to experience poorer overall quality of play, with particular deficits in social play. Considering play is a child's primary occupation, this finding becomes pertinent for occupational therapy practice, particularly in post-apartheid South Africa, where high prenatal alcohol exposure prevalence rates are couched within persistent socio-economic inequalities. © 2014 Occupational Therapy Australia.

Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

PubMed

Mantella, Nicole M; Youngentob, Steven L

2014-01-01

Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

Prenatal Alcohol Exposure Increases Postnatal Acceptability of Nicotine Odor and Taste in Adolescent Rats

PubMed Central

Mantella, Nicole M.; Youngentob, Steven L.

2014-01-01

Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation

PubMed Central

Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P.; Zhou, Feng C.

2009-01-01

Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88 mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10 and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p < 0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes

Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.

PubMed

Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P; Zhou, Feng C

2009-10-01

Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p<0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in

Prenatal exposure to vanilla or alcohol induces crawling after these odors in the neonate rat: The role of mu and kappa opioid receptor systems.

PubMed

Gaztañaga, Mirari; Aranda-Fernández, P Ezequiel; Chotro, M Gabriela

2015-09-01

Rat fetuses can perceive chemosensory stimuli derived from their mother's diet, and they may learn about those stimuli. In previous studies we have observed that prenatal exposure to alcohol during the last days of gestation increases the acceptance and liking of an alcohol flavor in infant and adolescent rats. While these results were not found after prenatal exposure to vanilla, cineole or anise, suggesting that the pharmacological properties of alcohol, mediated by the opioid system, underlie the effects observed with this drug. Considering that other studies report enhanced acceptance of non-alcohol flavors experienced prenatally when subjects were tested before infancy, we explore the possibility of observing similar results if testing 1-day old rats exposed prenatally to vanilla. Using an "odor-induced crawling" testing procedure, it was observed that neonates exposed prenatally to vanilla or alcohol crawl for a longer distance towards the experienced odor than to other odors or than control pups. Blocking mu, but not kappa opioid receptors, reduced the attraction of vanilla odor to neonates exposed to vanilla in utero, while the response to alcohol in pups exposed prenatally to this drug was affected by both antagonists. Results confirm that exposure to a non-alcohol odor enhances postnatal responses to it, observable soon after birth, while also suggesting that the mu opioid receptor system plays an important role in generating this effect. The results also imply that with alcohol exposure, the prenatal opioid system is wholly involved, which could explain the longer retention of the enhanced attraction to alcohol following prenatal experience with the drug. Copyright © 2014 Elsevier Inc. All rights reserved.

Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

PubMed

Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

2015-01-01

Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

Disclosure and Exposure of Alcohol on Social Media and Later Alcohol Use: A Large-Scale Longitudinal Study.

PubMed

Erevik, Eilin K; Torsheim, Torbjørn; Andreassen, Cecilie S; Vedaa, Øystein; Pallesen, Ståle

2017-01-01

This article aims to investigate whether alcohol-related disclosure and exposure on social media can predict later alcohol use, and to identify covariates in these relationships. Data were collected by online surveys (two waves) among students in Bergen, Norway. The first survey was administered in fall 2015. The follow-up took place during fall 2016. A total of 5,217 students participated in both waves. The surveys included questions about demographics, personality, alcohol use, alcohol-related cognitions (e.g., attitudes and norms), social media use, and disclosure and exposure of alcohol on social media. Bivariate comparisons were conducted to assess differences in alcohol use between the frequent (i.e., monthly or more often) disclosure and exposure groups and low-frequent disclosure and exposure groups. Crude and adjusted linear regressions were employed to investigate if disclosure and exposure of alcohol could predict later alcohol use, when controlling for a range of covariates. Compared to the low-frequent disclosure and exposure groups, participants which frequently disclosed or were frequently exposed to alcohol-related content had higher alcohol use at baseline and 1 year later ( p < 0.001), when no covariates were controlled for. Frequent disclosure of content reflecting positive aspects of alcohol predicted stable or slightly increased alcohol use at Time 2 ( p < 0.01), even when all covariates (i.e., demographics, personality, alcohol use, alcohol-related cognitions, and social media use) were controlled for. In conclusion, frequent disclosure and/or exposure to alcohol-related content predicted alcohol use over time. Alcohol disclosure/exposure on social media could for the most part not predict later alcohol use when baseline alcohol use was controlled for. High alcohol use and alcohol disclosure/exposure on social media appear to be strongly intertwined, which hampers identification of directionality between alcohol use and disclosure/exposure

Disclosure and Exposure of Alcohol on Social Media and Later Alcohol Use: A Large-Scale Longitudinal Study

PubMed Central

Erevik, Eilin K.; Torsheim, Torbjørn; Andreassen, Cecilie S.; Vedaa, Øystein; Pallesen, Ståle

2017-01-01

This article aims to investigate whether alcohol-related disclosure and exposure on social media can predict later alcohol use, and to identify covariates in these relationships. Data were collected by online surveys (two waves) among students in Bergen, Norway. The first survey was administered in fall 2015. The follow-up took place during fall 2016. A total of 5,217 students participated in both waves. The surveys included questions about demographics, personality, alcohol use, alcohol-related cognitions (e.g., attitudes and norms), social media use, and disclosure and exposure of alcohol on social media. Bivariate comparisons were conducted to assess differences in alcohol use between the frequent (i.e., monthly or more often) disclosure and exposure groups and low-frequent disclosure and exposure groups. Crude and adjusted linear regressions were employed to investigate if disclosure and exposure of alcohol could predict later alcohol use, when controlling for a range of covariates. Compared to the low-frequent disclosure and exposure groups, participants which frequently disclosed or were frequently exposed to alcohol-related content had higher alcohol use at baseline and 1 year later (p < 0.001), when no covariates were controlled for. Frequent disclosure of content reflecting positive aspects of alcohol predicted stable or slightly increased alcohol use at Time 2 (p < 0.01), even when all covariates (i.e., demographics, personality, alcohol use, alcohol-related cognitions, and social media use) were controlled for. In conclusion, frequent disclosure and/or exposure to alcohol-related content predicted alcohol use over time. Alcohol disclosure/exposure on social media could for the most part not predict later alcohol use when baseline alcohol use was controlled for. High alcohol use and alcohol disclosure/exposure on social media appear to be strongly intertwined, which hampers identification of directionality between alcohol use and disclosure/exposure

Adolescent alcohol exposure: Are there separable vulnerable periods within adolescence?

PubMed

Spear, Linda Patia

2015-09-01

There are two key alcohol use patterns among human adolescents that confer increased vulnerability for later alcohol abuse/dependence, along with neurocognitive alterations: (a) early initiation of use during adolescence, and (b) high rates of binge drinking that are particularly prevalent late in adolescence. The central thesis of this review is that lasting neurobehavioral outcomes of these two adolescent exposure patterns may differ. Although it is difficult to disentangle consequences of early use from later binge drinking in human studies given the substantial overlap between groups, these two types of problematic adolescent use are differentially heritable and hence separable to some extent. Although few studies using animal models have manipulated alcohol exposure age, those studies that have have typically observed timing-specific exposure effects, with more marked (or at least different patterns of) lasting consequences evident after exposures during early-mid adolescence than late-adolescence/emerging adulthood, and effects often restricted to male rats in those few instances where sex differences have been explored. As one example, adult male rats exposed to ethanol during early-mid adolescence (postnatal days [P] 25-45) were found to be socially anxious and to retain adolescent-typical ethanol-induced social facilitation into adulthood, effects that were not evident after exposure during late-adolescence/emerging adulthood (P45-65); exposure at the later interval, however, induced lasting tolerance to ethanol's social inhibitory effects that was not evident after exposure early in adolescence. Females, in contrast, were little influenced by ethanol exposure at either interval. Exposure timing effects have likewise been reported following social isolation as well as after repeated exposure to other drugs such as nicotine (and cannabinoids), with effects often, although not always, more pronounced in males where studied. Consistent with these timing

ADOLESCENT ALCOHOL EXPOSURE: ARE THERE SEPARABLE VULNERABLE PERIODS WITHIN ADOLESCENCE?

PubMed Central

Spear, Linda Patia

2015-01-01

There are two key alcohol use patterns among human adolescents that confer increased vulnerability for later alcohol abuse/dependence, along with neurocognitive alterations: (a) early initiation of use during adolescence, and (b) high rates of binge drinking that are particularly prevalent late in adolescence. The central thesis of this review is that lasting neurobehavioral outcomes of these two adolescent exposure patterns may differ. Although it is difficult to disentangle consequences of early use from later binge drinking in human studies given the substantial overlap between groups, these two types of problematic adolescent use are differentially heritable and hence separable to some extent. Although few studies using animal models have manipulated alcohol exposure age, those studies that have have typically observed timing-specific exposure effects, with more marked (or at least different patterns of) lasting consequences evident after exposures during early-mid adolescence than late-adolescence/emerging adulthood, and effects often restricted to male rats in those few instances where sex differences have been explored. As one example, adult male rats exposed to ethanol during early-mid adolescence (postnatal days [P] 25-45) were found to be socially anxious and to retain adolescent-typical ethanol-induced social facilitation into adulthood, effects that were not evident after exposure during late-adolescence/emerging adulthood (P45-65); exposure at the later interval, however, induced lasting tolerance to ethanol's social inhibitory effects that was not evident after exposure early in adolescence. Females, in contrast, were little influenced by ethanol exposure at either interval. Exposure timing effects have likewise been reported following social isolation as well as after repeated exposure to other drugs such as nicotine (and cannabinoids), with effects often, although not always, more pronounced in males where studied. Consistent with these timing

Ecological Momentary Assessment of the Association Between Exposure to Alcohol Advertising and Early Adolescents' Beliefs About Alcohol

PubMed Central

Martino, Steven C.; Kovalchik, Stephanie A.; Collins, Rebecca L.; Becker, Kirsten M.; Shadel, William G.; D'Amico, Elizabeth J.

2015-01-01

Purpose To evaluate the momentary association between exposure to alcohol advertising and middle school students' beliefs about alcohol in real-world settings and to explore racial/ethnic differences in this association. Methods Middle school students (N = 588) carried handheld data collection devices for 14 days, recording their exposures to all forms of alcohol advertising during the assessment period. Students also responded to three investigator-initiated control prompts (programmed to occur randomly) on each day of the assessment period. After each exposure to advertising and at each control prompt, students reported their beliefs about alcohol. Mixed effects regression models compared students' beliefs about alcohol between moments of exposure to alcohol advertising and control prompts. Results Students perceived the typical person their age who drinks alcohol (prototype perceptions) more favorably and perceived alcohol use as more normative at times of exposure to alcohol advertising than at times of non-exposure (i.e., at control prompts). Exposure to alcohol advertising was not associated with shifts in the perceived norms of Black and Hispanic students, however, and the association between exposure and prototype perceptions was stronger among non-Hispanic students than among Hispanic students. Conclusions Exposure to alcohol advertising is associated with acute shifts in adolescents' perceptions of the typical person that drinks alcohol and the normativeness of drinking. These associations are both statistically and substantively meaningful. PMID:26480846

The alcoholism generator.

PubMed

Miller, Michael W; Spear, Linda P

2006-09-01

Alcohol exposure largely affects 3 populations: fetuses, adolescents, and adults. These 3 developmental stages are inextricably intertwined such that elevated alcohol exposure at any time increases the probability of exposure at the others. This circular interdependency is called the alcoholism generator. Furthermore, exposure to large amounts of alcohol at these 3 times can cause cognitive dysfunction, largely through mechanisms of alcohol-induced perturbations in neurogenesis and synaptogenesis. Breaking this cycle is key to reducing problem alcohol drinking and the associated sequelae.

Moral maturity and delinquency after prenatal alcohol exposure.

PubMed

Schonfeld, Amy M; Mattson, Sarah N; Riley, Edward P

2005-07-01

Prenatal exposure to alcohol is associated with cognitive, behavioral and social deficits, including delinquency. Although delinquent populations and those with intellectual and behavioral deficits exhibit impaired moral judgment and reasoning, this area remains unexplored in alcohol-exposed individuals. Moral maturity and delinquency were evaluated in 27 participants with prenatal alcohol exposure (ALC group) and 29 nonexposed controls (CON group) matched on age (range: 10-18), gender, handedness, socioeconomic status and ethnicity. Moral maturity was evaluated using the Sociomoral Reflection Measure-Short Form, and delinquency was evaluated with the Conduct Disorder (CD) Questionnaire. Additional measures included social desirability and inhibition. The ALC group performed at a lower level of moral maturity than the CON group. Whereas Verbal IQ primarily predicted this difference, a deficit on the moral value judgment having to do with relationships with others was specific to prenatal alcohol exposure. Furthermore, delinquency was higher in the ALC group, and specific sociomoral values were predictive of delinquent behavior. Finally, half of the children and adolescents with a history of prenatal alcohol exposure but without fetal alcohol syndrome had probable CD. The results of this study indicate that interventions aimed at reducing delinquency in those with prenatal alcohol exposure are necessary, and targeting moral judgment for this purpose may be beneficial.

Ecological Momentary Assessment of the Association Between Exposure to Alcohol Advertising and Early Adolescents' Beliefs About Alcohol.

PubMed

Martino, Steven C; Kovalchik, Stephanie A; Collins, Rebecca L; Becker, Kirsten M; Shadel, William G; D'Amico, Elizabeth J

2016-01-01

To evaluate the momentary association between exposure to alcohol advertising and middle-school students' beliefs about alcohol in real-world settings and to explore racial/ethnic differences in this association. Middle-school students (N = 588) carried handheld data collection devices for 14 days, recording their exposures to all forms of alcohol advertising during the assessment period. Students also responded to three investigator-initiated control prompts (programmed to occur randomly) on each day of the assessment period. After each exposure to advertising and at each control prompt, students reported their beliefs about alcohol. Mixed-effects regression models compared students' beliefs about alcohol between moments of exposure to alcohol advertising and control prompts. Students perceived the typical person their age who drinks alcohol (prototype perceptions) more favorably and perceived alcohol use as more normative at times of exposure to alcohol advertising than at times of nonexposure (i.e., at control prompts). Exposure to alcohol advertising was not associated with shifts in the perceived norms of black and Hispanic students, however, and the association between exposure and prototype perceptions was stronger among non-Hispanic students than among Hispanic students. Exposure to alcohol advertising is associated with acute shifts in adolescents' perceptions of the typical person that drinks alcohol and the normativeness of drinking. These associations are both statistically and substantively meaningful. Copyright © 2016 Society for Adolescent Health and Medicine. All rights reserved.

Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets

PubMed Central

Krahe, Thomas E.; Filgueiras, Claudio C.; Medina, Alexandre E.

2017-01-01

Exposure to alcohol and valproic acid (VPA) during pregnancy can lead to fetal alcohol spectrum disorders and fetal valproate syndrome, respectively. Altered social behavior is a hallmark of both these conditions and there is ample evidence showing that developmental exposure to alcohol and VPA affect social behavior in rodents. However, results from rodent models are somewhat difficult to translate to humans owing to the substantial differences in brain development, morphology, and connectivity. Since the cortex folding pattern is closely related to its specialization and that social behavior is strongly influenced by cortical structures, here we studied the effects of developmental alcohol and VPA exposure on the play behavior of the ferret, a gyrencephalic animal known for its playful nature. Animals were injected with alcohol (3.5 g/kg, i.p.), VPA (200 mg/kg, i.p.) or saline (i.p) every other day during the brain growth spurt period, between postnatal days 10 and 30. The play behavior of pairs of the same experimental group was evaluated 3 weeks later. Both treatments induced significant behavioral differences compared to controls. Alcohol and VPA exposed ferrets played less than saline treated ones, but while animals from the alcohol group displayed a delay in start playing with each other, VPA treated ones spent most of the time close to one another without playing. These findings not only extend previous results on the effects of developmental exposure to alcohol and VPA on social behavior, but make the ferret a great model to study the underlying mechanisms of social interaction. PMID:27208641

Factors Associated with Younger Adolescents’ Exposure to Online Alcohol Advertising

PubMed Central

D’Amico, Elizabeth J.; Martino, Steven C.; Collins, Rebecca L.; Shadel, William G.; Tolpadi, Anagha; Kovalchik, Stephanie; Becker, Kirsten M.

2016-01-01

Little is known about the extent and nature of youth exposure to online alcohol advertising, or factors that may be associated with exposure. The current study recruited middle school students who completed a paper survey and then logged each alcohol advertisement that they encountered over a two-week period using cell phones as part of an ecological momentary assessment (EMA) design. We examined the percentage of youth who reported exposure to online alcohol advertising in the past two weeks, average weekly rate of exposure, types of online alcohol advertisements youth reported seeing, and factors that increased youths’ risk of exposure to online alcohol advertising. Analyses are based on 485 participants (47% female; 25% Hispanic, 25% white, 27% black; 6% Asian, 16% other). Youth logged exposures to a total of 3,966 (16,018 weighted for under-reporting) alcohol advertisements across the monitoring period; 154 (568 weighted) or 3.6% were online ads. Seventeen percent of youth reported seeing any online alcohol ad; the majority of online ads seen were video commercials (44.8%) and banner/side ads (26.6%). Factors associated with greater ad exposure were being older, rebellious, and Black race; greater parental monitoring and more hours spent on social media were associated with less exposure. Findings provide important information about adolescents’ exposure to online alcohol advertising and what might contribute to a greater likelihood of exposure. Given that online ad exposure is linked to drinking behavior, prevention programming for younger adolescents should continue to address this issue to help youth make healthy choices regarding alcohol use. PMID:27819430

Adolescent Binge Alcohol Exposure Affects the Brain Function Through Mitochondrial Impairment.

PubMed

Tapia-Rojas, Cheril; Carvajal, Francisco J; Mira, Rodrigo G; Arce, Camila; Lerma-Cabrera, José Manuel; Orellana, Juan A; Cerpa, Waldo; Quintanilla, Rodrigo A

2018-05-01

In the young population, binge drinking is a pattern of problematic alcohol consumption, characterized by a short period of heavy drinking followed by abstinence which is frequently repeated over time. This drinking pattern is associated with mental problems, use of other drugs, and an increased risk of excessive alcohol intake during adulthood. However, little is known about the effects of binge drinking on brain function in adolescents and its neurobiological impact during the adulthood. In the present study, we evaluated the effects of alcohol on hippocampal memory, synaptic plasticity, and mitochondrial function in adolescent rats after a binge drinking episode in vivo. These effects were analyzed at 1, 3, or 7 weeks post alcohol exposure. Our results showed that binge-like ethanol pre-treated (BEP) rats exhibited early alterations in learning and memory tests accompanied by an impairment of synaptic plasticity that was total and partially compensated, respectively. These changes could be attributed to a rapid increase in oxidative damage and a late inflammatory response induced by post ethanol exposure. Additionally, BEP alters the regulation of mitochondrial dynamics and modifies the expression of mitochondrial permeability transition pore (mPTP) components, such as cyclophilin D (Cyp-D) and the voltage-dependent anion channel (VDAC). These mitochondrial structural changes result in the impairment of mitochondrial bioenergetics, decreasing ATP production progressively until adulthood. These results strongly suggest that teenage alcohol binge drinking impairs the function of the adult hippocampus including memory and synaptic plasticity as a consequence of the mitochondrial damage induced by alcohol and that the recovery of hippocampal function could implicate the activation of alternative pathways that fail to reestablish mitochondrial function.

The party effect: Prediction of future alcohol use based on exposure to specific alcohol advertising content

PubMed Central

Morgenstern, Matthis; Li, Zhongze; Li, Zhigang; Sargent, James D.

2016-01-01

Aims To test whether exposure to party-related alcohol advertising is associated with drinking behavior in a national US sample of adolescents and young adults, independently of exposure to other alcohol advertising. Design Longitudinal telephone- and web-based surveys conducted in 2011 and 2013. Setting All regions of the United States, participants selected via mixed-mode random-digit-dial landline and cellphone frames. Participants A sample of 2541 respondents with a mean age of 18.1 years (51.6% female) of which 1053 (41%) never had a whole drink of alcohol and 1727 (67%) never had six or more drinks during one drinking occasion. Measurements Outcome measures were onset of alcohol use and binge drinking during the study interval. Primary predictor was exposure to television alcohol advertising, operationalized as contact frequency and brand recall for 20 randomly selected alcohol advertisements. Independent post-hoc analyses classified all ads as “party” or “non-party” ads. Sociodemographics, sensation seeking, alcohol expectancies, and alcohol use of friends and family were assessed as covariates. Findings Onset rates for having the first whole drink of alcohol and for first binge drinking were 49.2% and 29.5%, respectively. On average, about half (M = 10.2) of the 20 alcohol advertisements in each individual survey were “party” ads. If both types of exposures (“party” and “non-party”) were included in the regression model, only “party” exposure remained a significant predictor of alcohol use onset (AOR=19.17; 95%CI 3.72–98.79) and binge drinking onset (AOR=3.87; 95%CI 1.07–13.99) after covariate control. Conclusions Adolescents and young adults with higher exposure to alcohol advertisements using a partying theme had higher rates of alcohol use and binge drinking onset, even after control of exposure to other types of alcohol advertisements. PMID:27343140

The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

PubMed

Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

2015-01-01

We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish

PubMed Central

Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

2015-01-01

We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an “inverted V” dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure. PMID:26558894

The relationship between exposure to alcohol advertising in stores, owning alcohol promotional items, and adolescent alcohol use.

PubMed

Hurtz, Shannon Q; Henriksen, Lisa; Wang, Yun; Feighery, Ellen C; Fortmann, Stephen P

2007-01-01

This paper describes adolescents' exposure to alcohol advertising in stores and to alcohol-branded promotional items and their association with self-reported drinking. A cross-sectional survey was administered in non-tracked required courses to sixth, seventh, and eighth graders (n = 2125) in three California middle schools. Logistic regressions compared the odds of ever (vs. never) drinking and current (vs. ever) drinking after controlling for psychosocial and other risk factors for adolescent alcohol use. Two-thirds of middle school students reported at least weekly visits to liquor, convenience, or small grocery stores where alcohol advertising is widespread. Such exposure was associated with higher odds of ever drinking, but was not associated with current drinking. One-fifth of students reported owning at least one alcohol promotional item. These students were three times more likely to have ever tried drinking and 1.5 times more likely to report current drinking than students without such items. This study provides clear evidence of an association of adolescent drinking with weekly exposure to alcohol advertising in stores and with ownership of alcohol promotional items. Given their potential influence on adolescent drinking behaviour, retail ads, and promotional items for alcohol deserve further study.

Factors associated with younger adolescents' exposure to online alcohol advertising.

PubMed

D'Amico, Elizabeth J; Martino, Steven C; Collins, Rebecca L; Shadel, William G; Tolpadi, Anagha; Kovalchik, Stephanie; Becker, Kirsten M

2017-03-01

Little is known about the extent and nature of youth exposure to online alcohol advertising, or factors that may be associated with exposure. The current study recruited middle school students who completed a paper survey and then logged each alcohol advertisement that they encountered over a 2-week period using cell phones as part of an ecological momentary assessment design. We examined the percentage of youth who reported exposure to online alcohol advertising in the past 2 weeks, average weekly rate of exposure, types of online alcohol advertisements youth reported seeing, and factors that increased youths' risk of exposure to online alcohol advertising. Analyses are based on 485 participants (47% female; 25% Hispanic, 25% White, 27% Black; 6% Asian, 16% other). Youth logged exposures to a total of 3,966 (16,018 weighted for underreporting) alcohol advertisements across the monitoring period; 154 (568 weighted) or 3.6% were online ads. Seventeen percent of youth reported seeing any online alcohol ad; the majority of online ads seen were video commercials (44.8%) and banner/side ads (26.6%). Factors associated with greater ad exposure were being older, rebellious, and Black race; greater parental monitoring and more hours spent on social media were associated with less exposure. Findings provide important information about adolescents' exposure to online alcohol advertising and what might contribute to a greater likelihood of exposure. Given that online ad exposure is linked to drinking behavior, prevention programming for younger adolescents should continue to address this issue to help youth make healthy choices regarding alcohol use. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

DNA Methylation program in normal and alcohol-induced thinning cortex

PubMed Central

Öztürk, Nail Can; Resendiz, Marisol; Öztürk, Hakan; Zhou, Feng C.

2017-01-01

While cerebral underdevelopment is a hallmark of fetal alcohol spectrum disorders (FASD), the mechanism(s) guiding the broad cortical neurodevelopmental deficits are not clear. DNA methylation is known to regulate early development and tissue specification through gene regulation. Here, we examined DNA methylation in the onset of alcohol-induced cortical thinning in a mouse model of FASD. C57BL/6 (B6) mice were administered a 4% alcohol (v/v) liquid diet from embryonic (E) days 7–16, and their embryos were harvested at E17, along with isocaloric liquid diet and lab chow controls. Cortical neuroanatomy, neural phenotypes, and epigenetic markers of methylation were assessed using immunohistochemistry, Western blot, and methyl-DNA assays. We report that cortical thickness, neuroepithelial proliferation, and neuronal migration and maturity were found to be deterred by alcohol at E17. Simultaneously, DNA methylation, including 5-methylcytosine (5mC) and 5-hydroxcylmethylcytosine (5hmC), which progresses as an intrinsic program guiding normal embryonic cortical development, was severely affected by in utero alcohol exposure. The intricate relationship between cortical thinning and this DNA methylation program disruption is detailed and illustrated. DNA methylation, dynamic across the multiple cortical layers during the late embryonic stage, is highly disrupted by fetal alcohol exposure; this disruption occurs in tandem with characteristic developmental abnormalities, ranging from structural to molecular. Finally, our findings point to a significant question for future exploration: whether epigenetics guides neurodevelopment or whether developmental conditions dictate epigenetic dynamics in the context of alcohol-induced cortical teratogenesis. PMID:28433420

Effects of cue-exposure treatment on neural cue reactivity in alcohol dependence: a randomized trial.

PubMed

Vollstädt-Klein, Sabine; Loeber, Sabine; Kirsch, Martina; Bach, Patrick; Richter, Anne; Bühler, Mira; von der Goltz, Christoph; Hermann, Derik; Mann, Karl; Kiefer, Falk

2011-06-01

In alcohol-dependent patients, alcohol-associated cues elicit brain activation in mesocorticolimbic networks involved in relapse mechanisms. Cue-exposure based extinction training (CET) has been shown to be efficacious in the treatment of alcoholism; however, it has remained unexplored whether CET mediates its therapeutic effects via changes of activity in mesolimbic networks in response to alcohol cues. In this study, we assessed CET treatment effects on cue-induced responses using functional magnetic resonance imaging (fMRI). In a randomized controlled trial, abstinent alcohol-dependent patients were randomly assigned to a CET group (n = 15) or a control group (n = 15). All patients underwent an extended detoxification treatment comprising medically supervised detoxification, health education, and supportive therapy. The CET patients additionally received nine CET sessions over 3 weeks, exposing the patient to his/her preferred alcoholic beverage. Cue-induced fMRI activation to alcohol cues was measured at pretreatment and posttreatment. Compared with pretreatment, fMRI cue-reactivity reduction was greater in the CET relative to the control group, especially in the anterior cingulate gyrus and the insula, as well as limbic and frontal regions. Before treatment, increased cue-induced fMRI activation was found in limbic and reward-related brain regions and in visual areas. After treatment, the CET group showed less activation than the control group in the left ventral striatum. The study provides first evidence that an exposure-based psychotherapeutic intervention in the treatment of alcoholism impacts on brain areas relevant for addiction memory and attentional focus to alcohol-associated cues and affects mesocorticolimbic reward pathways suggested to be pathophysiologically involved in addiction. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Potential Role of the Gut/Liver/Lung Axis in Alcohol-Induced Tissue Pathology

PubMed Central

Massey, Veronica L.; Beier, Juliane I.; Ritzenthaler, Jeffrey D.; Roman, Jesse; Arteel, Gavin E.

2015-01-01

Both Alcoholic Liver Disease (ALD) and alcohol-related susceptibility to acute lung injury are estimated to account for the highest morbidity and mortality related to chronic alcohol abuse and, thus, represent a focus of intense investigation. In general, alcohol-induced derangements to both organs are considered to be independent and are often evaluated separately. However, the liver and lung share many general responses to damage, and specific responses to alcohol exposure. For example, both organs possess resident macrophages that play key roles in mediating the immune/inflammatory response. Additionally, alcohol-induced damage to both organs appears to involve oxidative stress that favors tissue injury. Another mechanism that appears to be shared between the organs is that inflammatory injury to both organs is enhanced by alcohol exposure. Lastly, altered extracellular matrix (ECM) deposition appears to be a key step in disease progression in both organs. Indeed, recent studies suggest that early subtle changes in the ECM may predispose the target organ to an inflammatory insult. The purpose of this chapter is to review the parallel mechanisms of liver and lung injury in response to alcohol consumption. This chapter will also explore the potential that these mechanisms are interdependent, as part of a gut-liver-lung axis. PMID:26437442

Movie Exposure to Alcohol Cues and Adolescent Alcohol Problems: A Longitudinal Analysis in a National Sample

PubMed Central

Wills, Thomas A.; Sargent, James D.; Gibbons, Frederick X.; Gerrard, Meg; Stoolmiller, Mike

2009-01-01

The authors tested a theoretical model of how exposure to alcohol cues in movies predicts level of alcohol use (ever use plus ever and recent binge drinking) and alcohol-related problems. A national sample of younger adolescents was interviewed by telephone with 4 repeated assessments spaced at 8-month intervals. A structural equation modeling analysis performed for ever-drinkers at Time 3 (N = 961) indicated that, controlling for a number of covariates, movie alcohol exposure at Time 1 was related to increases in peer alcohol use and adolescent alcohol use at Time 2. Movie exposure had indirect effects to alcohol use and problems at Times 3 and 4 through these pathways, with direct effects to problems from Time 1 rebelliousness and Time 2 movie exposure also found. Prospective risk-promoting effects were also found for alcohol expectancies, peer alcohol use, and availability of alcohol in the home; protective effects were found for mother’s responsiveness and for adolescent’s school performance and self-control. Theoretical and practical implications are discussed. PMID:19290687

Movie exposure to alcohol cues and adolescent alcohol problems: a longitudinal analysis in a national sample.

PubMed

Wills, Thomas A; Sargent, James D; Gibbons, Frederick X; Gerrard, Meg; Stoolmiller, Mike

2009-03-01

The authors tested a theoretical model of how exposure to alcohol cues in movies predicts level of alcohol use (ever use plus ever and recent binge drinking) and alcohol-related problems. A national sample of younger adolescents was interviewed by telephone with 4 repeated assessments spaced at 8-month intervals. A structural equation modeling analysis performed for ever-drinkers at Time 3 (N = 961) indicated that, controlling for a number of covariates, movie alcohol exposure at Time 1 was related to increases in peer alcohol use and adolescent alcohol use at Time 2. Movie exposure had indirect effects to alcohol use and problems at Times 3 and 4 through these pathways, with direct effects to problems from Time 1 rebelliousness and Time 2 movie exposure also found. Prospective risk-promoting effects were also found for alcohol expectancies, peer alcohol use, and availability of alcohol in the home; protective effects were found for mother's responsiveness and for adolescent's school performance and self-control. Theoretical and practical implications are discussed. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.

PubMed

Ji, Cheng

2014-01-01

Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also  in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.

The party effect: prediction of future alcohol use based on exposure to specific alcohol advertising content.

PubMed

Morgenstern, Matthis; Li, Zhongze; Li, Zhigang; Sargent, James D

2017-01-01

To test whether exposure to party-related alcohol advertising is associated with drinking behavior in a national US sample of adolescents and young adults, independently of exposure to other alcohol advertising. Longitudinal telephone- and web-based surveys conducted in 2011 and 2013. All regions of the United States, participants selected via mixed-mode random-digit-dial landline and cellphone frames. A sample of 705 respondents who never had a whole drink of alcohol at baseline (mean age 16.9 years, 53.3% female) and a sample of 1036 who never had six or more drinks during one drinking occasion (mean age 17.4 years, 55.8% female). Outcome measures were onset of alcohol use and binge drinking during the study interval. Primary predictor was exposure to television alcohol advertising, operationalized as contact frequency and brand recall for 20 randomly selected alcohol advertisements. Independent post-hoc analyses classified all advertisements as 'party' or 'non-party' advertisements. Socio-demographics, sensation-seeking, alcohol expectancies and alcohol use of friends and family were assessed as covariates. Onset rates for having the first whole drink of alcohol and for first binge drinking were 49.2% and 29.5%, respectively. On average, approximately half (median = 10.2) of the 20 alcohol advertisements in each individual survey were 'party' advertisements. If both types of exposures ('party' and 'non-party') were included in the regression model, only 'party' exposure remained a significant predictor of alcohol use onset [adjusted odds ratio (AOR) = 19.17; 95% confidence interval (CI) = 3.72-98.79] and binge drinking onset (AOR = 3.87; 95% CI = 1.07-13.99) after covariate control. Adolescents and young adults in the United States appear to have higher rates of alcohol use and binge drinking onset if they have higher exposure to alcohol advertisements using a partying theme, independently of the amount of exposure to alcohol advertisements with non

Effects of prenatal alcohol exposure on testosterone and pubertal development

PubMed Central

Carter, R.C.; Jacobson, J.L.; Dodge, N.C.; Granger, D.A.; Jacobson, S.W.

2014-01-01

Background Animal models have demonstrated fetal alcohol-related disruptions in neuroendocrine function in the hypothalamic-pituitary-gonadal (HPG) axis and downstream effects on pubertal development and sexual behavior in males and females, but little is known about these effects in humans. This study examined whether prenatal alcohol exposure is associated with alterations in testosterone during adolescence and whether it affects timing of pubertal development. Methods The sample consisted of 265 African American adolescents from the Detroit Longitudinal Cohort Study for whom testosterone and/or pubertal development data were available. Subjects were offspring of women recruited at their first prenatal clinic visit to over-represent moderate-to-heavy alcohol use, including a 5% random sample of low-level drinkers/abstainers. Mothers were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach and about their smoking and drug use and sociodemographic factors. At age 14 years, adolescents provided salivary samples, which were analyzed for testosterone (pg/mL), self-reported Tanner stages for pubertal development, and age at menarche (females). Results Prenatal alcohol exposure was related to elevated testosterone concentrations for males and females but not to changes in Tanner stages or age at menarche, after controlling for confounders. In regression models stratified by alcohol exposure, the expected relation between testosterone and pubic hair development was seen among males with light-to-no prenatal alcohol exposure but not among those with moderate-to-heavy prenatal alcohol exposure. This interaction between testosterone and prenatal alcohol exposure was confirmed in multivariable models including an alcohol exposure group X testosterone interaction term and potential confounders. Conclusions This study was the first to show a relation between prenatal alcohol exposure and increased testosterone during

Interactive effects of prenatal exposure to restraint stress and alcohol on pentylenetetrazol-induced seizure behaviors in rat offspring.

PubMed

Hashemi, Paria; Roshan-Milani, Shiva; Saboory, Ehsan; Ebrahimi, Loghman; Soltanineghad, Maryam

2016-11-01

Prenatal exposure to stress or alcohol increases vulnerability of brain regions involved in neurobehavioral development and programs susceptibility to seizure. To examine how prenatal alcohol interferes with stress-sensitive seizures, corticosterone (COS) blood levels and pentylenetetrazol (PTZ)-induced seizure behaviors were investigated in rat pups, prenatally exposed to stress, alcohol, or both. Pregnant rats were exposed to stress and saline/alcohol on 17, 18, and 19 days of pregnancy and divided into four groups of control-saline (CS), control-alcohol (CA), restraint stress-saline (RS), and restraint stress-alcohol (RA). In CS/CA groups, rats received saline/alcohol (20%, 2 g/kg, intraperitoneally [i.p.]). In RS/RA groups, rats were exposed to restraint stress by being held immobile in a Plexiglas ® tube (twice/day, 1 h/session), and received saline/alcohol, simultaneously. After parturition, on postnatal days 6 and 15 (P6 & P15), blood samples were collected from the pups to determine COS level. On P15 and P25, PTZ (45 mg/kg) was injected into the rest of the pups and seizure behaviors were then recorded. COS levels increased in pups of the RS group but not in pups of the RA group. Both focal and tonic-clonic seizures were prevalent and severe in pups of the RS group, whereas only focal seizures were prominent in pups of the CA group. However, pups prenatally exposed to co-administration of alcohol and stress, unexpectedly, did not show additive epileptic effects. The failure of pups prenatally exposed to alcohol to show progressive or facilitatory epileptic responses to stressors, indicates decreased plasticity and adaptability, which may negatively affect HPA-axis performance or hippocampal structure/function. Copyright © 2016 Elsevier Inc. All rights reserved.

Photobiomodulation on alcohol induced dysfunction

NASA Astrophysics Data System (ADS)

Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

2007-05-01

Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

THE RELATIONSHIP BETWEEN EXPOSURE TO ALCOHOL ADVERTISING IN STORES, OWNING ALCOHOL PROMOTIONAL ITEMS, AND ADOLESCENT ALCOHOL USE

PubMed Central

HURTZ, SHANNON Q.; HENRIKSEN, LISA; WANG, YUN; FEIGHERY, ELLEN C.; FORTMANN, STEPHEN P.

2014-01-01

Aim This paper describes adolescents’ exposure to alcohol advertising in stores and to alcohol-branded promotional items and their association with self-reported drinking. Methods A cross-sectional survey was administered in non-tracked required courses to sixth, seventh, and eighth graders (n = 2125) in three California middle schools. Logistic regressions compared the odds of ever (vs. never) drinking and current (vs. ever) drinking after controlling for psychosocial and other risk factors for adolescent alcohol use. Results Two-thirds of middle school students reported at least weekly visits to liquor, convenience, or small grocery stores where alcohol advertising is widespread. Such exposure was associated with higher odds of ever drinking, but was not associated with current drinking. One-fifth of students reported owning at least one alcohol promotional item. These students were three times more likely to have ever tried drinking and 1.5 times more likely to report current drinking than students without such items. Conclusions This study provides clear evidence of an association of adolescent drinking with weekly exposure to alcohol advertising in stores and with ownership of alcohol promotional items. Given their potential influence on adolescent drinking behaviour, retail ads, and promotional items for alcohol deserve further study. PMID:17218364

Media exposure and marijuana and alcohol use among adolescents.

PubMed

Primack, Brian A; Kraemer, Kevin L; Fine, Michael J; Dalton, Madeline A

2009-01-01

We aimed to determine which media exposures are most strongly associated with marijuana and alcohol use among adolescents. In 2004, we surveyed 1,211 students at a large high school in suburban Pittsburgh regarding substance use, exposure to entertainment media, and covariates. Of the respondents, 52% were female, 8% were non-White, 27% reported smoking marijuana, and 60% reported using alcohol. They reported average exposure to 8.6 hr of media daily. In adjusted models, exposure to music was independently associated with marijuana use, but exposure to movies was independently associated with alcohol use. Implications, limitations, and suggestions for further research are discussed.

Exposure to alcohol during adolescence exerts long-term effects on stress response and the adult brain stress circuits.

PubMed

Allen, Camryn D; Grigoleit, Jan-Sebastian; Hong, Joonho; Bae, Sejin; Vaughan, Joan; Lee, Soon

2016-12-17

The hypothalamic-pituitary-adrenal (HPA) axis undergoes critical developments during adolescence. Therefore, stressors experienced during this period potentially have long-term effects on adult HPA axis function. We hypothesized that adolescent intermittent ethanol (AIE) exposure would affect adult HPA axis function, resulting in altered responses to an alcohol challenge in young adults or adults. To test these hypotheses, male rats were exposed to alcohol vapor for 6h per day from post-natal day (PND) 28-42, then acutely challenged with alcohol intragastrically (3.2-4.5g/kg) in young adults (PND 70) or adults (PND 90). Overall, we observed blunted HPA axis responses to an alcohol challenge due to AIE exposure. Specifically, AIE tended to inhibit the alcohol challenge-induced increase in plasma corticosterone (CORT) concentrations in young adult and adult rats. As well, AIE significantly blunted the alcohol challenge-induced arginine vasopressin (Avp) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus of adult rats. Results of the present study are similar to what we have previously shown, that these changes in PVN responsiveness may result from AIE-induced alterations in adrenergic neurons in brain stem regions C1-C3 known to project to the PVN. AIE elevated the number of colocalized c-fos/phenylethanolamine N-methyltransferase (PNMT)-positive cell bodies in the C1 region of adult rats. Together, these data suggest that AIE exposure produces alterations in male HPA axis responsiveness to administration of an acute alcohol challenge that may be long-lasting. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of prenatal alcohol and cigarette exposure on offspring substance use in multiplex, alcohol-dependent families.

PubMed

O'Brien, Jessica W; Hill, Shirley Y

2014-12-01

Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use. A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High-risk families were selected based on the presence of 2 alcohol-dependent sisters. Low-risk families were selected on the basis of minimal first and second-degree relatives with AD. High-risk (HR = 99) and Low-risk offspring (LR = 110) were assessed annually during childhood and biennially in young adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit, mothers were interviewed concerning their prenatal use of substances. High-risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than low-risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD. Women with a family history of

Increased expression of protein kinase A inhibitor alpha (PKI-alpha) and decreased PKA-regulated genes in chronic intermittent alcohol exposure.

PubMed

Repunte-Canonigo, Vez; Lutjens, Robert; van der Stap, Lena D; Sanna, Pietro Paolo

2007-03-23

Intermittent models of alcohol exposure that mimic human patterns of alcohol consumption produce profound physiological and biochemical changes and induce rapid increases in alcohol self-administration. We used high-density oligonucleotide microarrays to investigate gene expression changes during chronic intermittent alcohol exposure in three brain regions that receive mesocorticolimbic dopaminergic projections and that are believed to be involved in alcohol's reinforcing actions: the medial prefrontal cortex, the nucleus accumbens and the amygdala. An independent replication of the experiment was used for RT-PCR validation of the microarray results. The protein kinase A inhibitor alpha (PKI-alpha, Pkia), a member of the endogenous PKI family implicated in reducing nuclear PKA activity, was found to be increased in all three regions tested. Conversely, we observed a downregulation of the expression of several PKA-regulated transcripts in one or more of the brain regions studied, including the activity and neurotransmitter-regulated early gene (Ania) - 1, -3, -7, -8, the transcription factors Egr1 and NGFI-B (Nr4a1) and the neuropeptide NPY. Reduced expression of PKA-regulated genes in mesocorticolimbic projection areas may have motivational significance in the rapid increase in alcohol self-administration induced by intermittent alcohol exposure.

Child and adolescent exposure to alcohol advertising in Australia's major televised sports.

PubMed

Carr, Sherilene; O'Brien, Kerry S; Ferris, Jason; Room, Robin; Livingston, Michael; Vandenberg, Brian; Donovan, Robert J; Lynott, Dermot

2016-07-01

Exposure to alcohol advertising is associated with greater alcohol consumption in children and adolescents, and alcohol advertising is common in Australian sport. We examine child, adolescent and young adult exposure to alcohol advertising during three televised sports in Australia: Australian Football League (AFL), cricket and the National Rugby League (NRL). Alcohol advertising and audience viewing data were purchased for all AFL, cricket and NRL TV programs in Australia for 2012. We estimated children and adolescents (0-17 years) and young adults (18-29 years) exposure to alcohol advertising during AFL, cricket and NRL programs in the daytime (06:00-20:29 h), and night-time (20:30-23:59 h). There were 3544 alcohol advertisements in AFL (1942), cricket (941) and NRL programs (661), representing 60% of all alcohol advertising in sport TV, and 15% of all alcohol advertisements on Australian TV. These programs had a cumulative audience of 26.9 million children and adolescents, and 32 million young adults. Children and adolescents received 51 million exposures to alcohol advertising, with 47% of this exposure occurring during the daytime. Children and adolescents exposure to alcohol advertising was similar to young adults and peaked after 8.30pm. Child and adolescent and young adult's exposure to alcohol advertising is high when viewing sport TV in Australia in the daytime and night-time. Current alcohol advertising regulations are not protecting children and adolescents from exposure, particularly in prominent televised sports. The regulations should be changed to reduce children and adolescent excessive exposure to alcohol advertising when watching sport. [Carr S, O'Brien KS, Ferris J, Room R, Livingston M, Vandenberg B, Donovan RJ, Lynott D. Child and adolescent exposure to alcohol advertising in Australia's major televised sports. Drug Alcohol Rev 2016;35:406-411]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Prenatal alcohol exposure increases the susceptibility to develop aggressive prolactinomas in the pituitary gland.

PubMed

Jabbar, Shaima; Reuhl, Kenneth; Sarkar, Dipak K

2018-05-16

Excess alcohol use is known to promote development of aggressive tumors in various tissues in human patients, but the cause of alcohol promotion of tumor aggressiveness is not clearly understood. We used an animals model of fetal alcohol exposure that is known to promote tumor development and determined if alcohol programs the pituitary to acquire aggressive prolactin-secreting tumors. Our results show that pituitaries of fetal alcohol-exposed rats produced increased levels of intra-pituitary aromatase protein and plasma estrogen, enhanced pituitary tissue growth, and upon estrogen challenge developed prolactin-secreting tumors (prolactinomas) that were hemorrhagic and often penetrated into the surrounding tissue. Pituitary tumors of fetal alcohol-exposed rats produced higher levels of hemorrhage-associated genes and proteins and multipotency genes and proteins. Cells of pituitary tumor of fetal alcohol exposed rat grew into tumor spheres in ultra-low attachment plate, expressed multipotency genes, formed an increased number of colonies, showed enhanced cell migration, and induced solid tumors following inoculation in immunodeficient mice. These data suggest that fetal alcohol exposure programs the pituitary to develop aggressive prolactinoma after estrogen treatment possibly due to increase in stem cell niche within the tumor microenvironment.

Gestational Alcohol Exposure Altered DNA Methylation Status in the Developing Fetus

PubMed Central

Mandal, Chanchal; Halder, Debasish; Jung, Kyoung Hwa; Chai, Young Gyu

2017-01-01

Ethanol is well known as a teratogenic factor that is capable of inducing a wide range of developmental abnormalities if the developing fetus is exposed to it. Duration and dose are the critical parameters of exposure that affect teratogenic variation to the developing fetus. It is suggested that ethanol interferes with epigenetic processes especially DNA methylation. We aimed to organize all of the available information on the alteration of DNA methylation by ethanol in utero. Thus, we have summarized all published information regarding alcohol-mediated alterations in DNA methylation during gestation. We tried to arrange information in a way that anyone can easily find the alcohol exposure time, doses, sampling time, and major changes in genomic level. Manuscript texts will also represent the correlation between ethanol metabolites and subsequent changes in methylome patterns. We hope that this review will help future researchers to further examine the issues associated with ethanol exposure. PMID:28657590

Toxic effects of prenatal exposure to alcohol, tobacco and other drugs.

PubMed

Scott-Goodwin, A C; Puerto, M; Moreno, I

2016-06-01

Tobacco, alcohol, cannabis and cocaine are the most consumed psychoactive drugs throughout the population. Prenatal exposure to these drugs could alter normal foetal development and could threaten future welfare. The main changes observed in prenatal exposure to tobacco are caused by nicotine and carbon monoxide, which can impede nutrient and oxygen exchange between mother and foetus, restricting foetal growth. Memory, learning processes, hearing and behaviour can also be affected. Alcohol may cause physical and cognitive alterations in prenatally exposed infants, fundamentally caused by altered NMDAR and GABAR activity. Tetrahydrocannabinol, the psychoactive compound of cannabis, is capable of activating CB1R, inducing connectivity deficits during the foetal brain development. This fact could be linked to behavioural and cognitive deficits. Many of the effects from prenatal cocaine exposure are caused by altered cell proliferation, migration, differentiation and dendritic growth processes. Cocaine causes long term behavioural and cognitive alterations and also affects the uteroplacental unit. Copyright © 2016 Elsevier Inc. All rights reserved.

Media Exposure and Marijuana and Alcohol Use Among Adolescents

PubMed Central

PRIMACK, BRIAN A.; KRAEMER, KEVIN L.; FINE, MICHAEL J.; DALTON, MADELINE A.

2010-01-01

We aimed to determine which media exposures are most strongly associated with marijuana and alcohol use among adolescents. In 2004, we surveyed 1,211 students at a large high school in suburban Pittsburgh regarding substance use, exposure to entertainment media, and covariates. Of the respondents, 52% were female, 8% were non-White, 27% reported smoking marijuana, and 60% reported using alcohol. They reported average exposure to 8.6 hr of media daily. In adjusted models, exposure to music was independently associated with marijuana use, but exposure to movies was independently associated with alcohol use. Implications, limitations, and suggestions for further research are discussed. PMID:19306219

Alcohol Exposure During Late Adolescence Increases Drinking in Adult Wistar Rats, an Effect that is not Reduced by Finasteride

PubMed Central

Milivojevic, Verica; Covault, Jonathan

2013-01-01

Aims: We tested whether an exposure to alcohol in late adolescence, an age of rapid increase in neuroactive steroid precursors, would increase voluntary alcohol consumption in adult rats and whether this effect would be modulated by finasteride, an inhibitor of neuroactive steroid synthesis. Methods: In Experiment 1, we exposed male Wistar rats to 8% alcohol during the dark cycle for 1 week during late adolescence [postnatal days (PNDs) 51–58], and then measured voluntary alcohol consumption 1 month later in adulthood (PNDs 91–104). In Experiment 2, finasteride was administered during the forced alcohol exposure in late adolescence and, in Experiment 3, during voluntary alcohol consumption in adulthood. Plasma was collected at the end of each finasteride treatment to confirm the reduction of plasma neuroactive steroid levels. Results: We found that a daily 12-h exposure to alcohol for 7 days in late adolescence significantly increased voluntary alcohol consumption (4-fold) a month later during adulthood. Finasteride administration in late adolescence increased group alcohol intake in late adolescence but did not block the effect of adolescent alcohol exposure on increasing alcohol preference in adulthood. There was no effect of finasteride treatment in adulthood on alcohol preference. Conclusions: A daily 12-h exposure to alcohol for 7 days in late adolescence was sufficient to induce chronically increased alcohol preference in adulthood, indicating that this age may be sensitive to the effects of alcohol. PMID:22997410

Perinatal choline supplementation does not mitigate motor coordination deficits associated with neonatal alcohol exposure in rats.

PubMed

Thomas, Jennifer D; O'Neill, Teresa M; Dominguez, Hector D

2004-01-01

Prenatal alcohol exposure can disrupt brain development, leading to a variety of behavioral alterations including learning deficits, hyperactivity, and motor dysfunction. We have been investigating the possibility that perinatal choline supplementation may effectively reduce the severity of alcohol's adverse effects on behavioral development. We previously reported that perinatal choline supplementation can ameliorate alcohol-induced learning deficits and hyperactivity in rats exposed to alcohol during development. The present study examined whether perinatal choline supplementation could also reduce the severity of motor deficits induced by alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4 to 9 via an artificial rearing procedure. Artificially and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4 to 30, whereas the other half received saline vehicle injections. On PD 35-37, subjects were tested on a parallel bar motor task, which requires both balance and fine motor coordination. Ethanol-exposed subjects exhibited significant motor impairments compared to both control groups whose performance did not differ significantly from one another. Perinatal choline treatment did not affect motor performance in either ethanol or control subjects. These data indicate that the beneficial effects of perinatal choline supplementation in ethanol-treated subjects are task specific and suggest that choline is more effective in mitigating cognitive deficits compared to motor deficits associated with developmental alcohol exposure.

Sex differences in adolescent exposure to alcohol advertising in magazines.

PubMed

Jernigan, David H; Ostroff, Joshua; Ross, Craig; O'Hara, James A

2004-07-01

To measure girls' and boys' exposure to alcohol advertising in magazines and to compare this exposure with that of legal-age persons. Alcohol advertisements (N = 6239) in 103 national magazines for which placement, audience, and cost data for 2001 and 2002 were available, categorized by year, beverage type, and brand. Placement and readership (age and sex) data generated estimates of media exposure for the age groups 12 to 20, 21 to 34, and 21 years and older. Gross rating points, an advertising industry standard measure of the level of media exposure of a given population, and gross rating point ratios comparing exposure of different demographic groups. Alcohol companies spent 590.4 million US dollars to place 471 beer and ale advertisements (8%), 4748 distilled spir-its advertisements (76%), 116 low-alcohol refresher advertisements (2%), and 904 advertisements for wine (14%) in magazines in 2001 and 2002. In 2002, underage youth saw 45% more beer and ale advertising, 12% more distilled spirits advertising, 65% more low-alcohol refresher advertising, and 69% less advertising for wine than persons 21 years and older. Girls aged 12 to 20 years were more likely to be exposed to beer, ale, and low-alcohol refresher advertising than women in the group aged 21 to 34 or women in the group aged 21 years and older. Girls' exposure to low-alcohol refresher advertising increased by 216% from 2001 to 2002, while boys' exposure increased 46%. Exposure of underage girls to alcohol advertising is substantial and increasing, pointing to the failure of industry self-regulation and the need for further action.

Psychiatric Conditions Associated with Prenatal Alcohol Exposure

ERIC Educational Resources Information Center

O'Connor, Mary J.; Paley, Blair

2009-01-01

Since the identification of fetal alcohol syndrome (FAS) over 35 years ago, mounting evidence about the impact of maternal alcohol consumption during pregnancy has prompted increased attention to the link between prenatal alcohol exposure (PAE) and a constellation of developmental disabilities that are characterized by physical, cognitive, and…

A Critical Role of Lateral Hypothalamus in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence

PubMed Central

Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M.; Bonci, Antonello

2014-01-01

In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. PMID:24872550

Exposure to Alcohol Content in Movies and Initiation of Early Drinking Milestones.

PubMed

Jackson, Kristina M; Janssen, Tim; Barnett, Nancy P; Rogers, Michelle L; Hayes, Kerri L; Sargent, James

2018-01-01

Exposure to alcohol content in movies has been shown to be associated with adolescent use of alcohol, including earlier onset. This study examined the influence of movie alcohol exposure on subsequent alcohol onset, considering the social context (whether the movie was viewed with a friend or parent). We examined whether media's influence holds across a spectrum of early drinking milestones: sipping (but not consuming a full drink of) alcohol, consuming a full drink of alcohol, and engaging in heavy episodic drinking (HED). Data were taken from a sample of 882 middle school youth (52% female; 24% non-White) enrolled in an ongoing study on alcohol initiation and progression. Exposure to alcohol content in films was measured using a method that combines content analysis and random assignment of movie titles to youth surveys. The hazard of initiating alcohol use (sip, full drink, HED) as a function of exposure was estimated using survival analysis. Associations were adjusted for demographic, personality, and social influence factors known to be associated with both movie exposure and alcohol use. Exposure to alcohol content was common. Hours of exposure prospectively predicted earlier onset of alcohol involvement across all outcomes. Viewing movies with friends appeared to augment the media exposure effect, in contrast to viewing movies with parents, which was not a significant predictor of initiation. Exposure to alcohol in films is involved in the entry into early stages of alcohol involvement. Findings support further investigation into the role of the media in underage drinking, especially in the context of consuming media with friends and peers. Limiting media exposure and/or stronger Federal Trade Commission oversight of movie ratings should be a priority for preventing underage drinking. Copyright © 2017 by the Research Society on Alcoholism.

Chronic alcohol feeding potentiates hormone-induced calcium signalling in hepatocytes.

PubMed

Bartlett, Paula J; Antony, Anil Noronha; Agarwal, Amit; Hilly, Mauricette; Prince, Victoria L; Combettes, Laurent; Hoek, Jan B; Gaspers, Lawrence D

2017-05-15

Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined. We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca 2+ -mobilizing hormones resulting in a leftward shift in the concentration-response relationship and the transition from oscillatory to more sustained and prolonged Ca 2+ increases. Our data demonstrate that alcohol-dependent adaptation in the Ca 2+ signalling pathway occurs at the level of hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) production and does not involve changes in the sensitivity of the IP 3 receptor or size of internal Ca 2+ stores. We suggest that prolonged and aberrant hormone-evoked Ca 2+ increases may stimulate the production of mitochondrial reactive oxygen species and contribute to alcohol-induced hepatocyte injury. ABSTRACT: 'Adaptive' responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide-dependent cytosolic calcium ([Ca 2+ ] i ) increases, which can adversely affect mitochondrial Ca 2+ levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose-response for Ca 2+ -mobilizing hormones resulting in more sustained and prolonged [Ca 2+ ] i increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca 2+ increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. Acute alcohol treatment (25 mm) completely inhibited hormone-induced calcium increases in control livers, but not after chronic alcohol-feeding, suggesting desensitization to the inhibitory actions of ethanol. Hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) accumulation and phospholipase C

Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories.

PubMed

von der Goltz, Christoph; Vengeliene, Valentina; Bilbao, Ainhoa; Perreau-Lenz, Stephanie; Pawlak, Cornelius R; Kiefer, Falk; Spanagel, Rainer

2009-08-01

In humans, the retrieval of memories associated with an alcohol-related experience frequently evokes alcohol-seeking behaviour. The reconsolidation hypothesis states that a consolidated memory could again become labile and susceptible to disruption after memory retrieval. The aim of our study was to examine whether retrieval of alcohol-related memories undergoes a reconsolidation process. For this purpose, male Wistar rats were trained to self-administer ethanol in the presence of specific conditioned stimuli. Thereafter, animals were left undisturbed in their home cages for the following 21 days. Memory retrieval was performed in a single 5-min exposure to all alcohol-associated stimuli. The protein synthesis inhibitor anisomycin, the non-competitive N-methyl-D: -aspartate (NMDA) receptor antagonist MK-801 and acamprosate, a clinically used drug known to reduce a hyper-glutamatergic state, were given immediately after retrieval of alcohol-related memories. The impact of drug treatment on cue-induced alcohol-seeking behaviour was measured on the following day and 7 days later. Administration of both anisomycin and MK-801 reduced cue-induced alcohol-seeking behaviour, showing that memory reconsolidation was disrupted by these compounds. However, acamprosate had no effect on the reconsolidation process, suggesting that this process is not dependent on a hyper-glutamatergic state but is more related to protein synthesis and NMDA receptor activity. Pharmacological disruption of reconsolidation of alcohol-associated memories can be achieved by the use of NMDA antagonists and protein synthesis inhibitors and may thus provide a potential new therapeutic strategy for the prevention of relapse in alcohol addiction.

Long-term cognitive, emotional and neurogenic alterations induced by alcohol and methamphetamine exposure in adolescent rats.

PubMed

Loxton, David; Canales, Juan J

2017-03-06

A high proportion of young methamphetamine (MA) users simultaneously consume alcohol. However, the potential neurological and behavioural alterations induced by such a drug combination have not been systematically examined. We studied in adolescent rats the long-term effects of alcohol, MA, and alcohol and MA combined on anxiety-like behaviour, memory, and neurogenesis in the adult hippocampus. Rats received saline, ethanol (ETOH, 1.5g/kg), MA (MA, 2mg/kg), or ethanol and MA combined (ETHOH-MA, 1.5g/kg ethanol plus 2mg/kg MA) via oral gavage, once daily for 5 consecutive days. Open field (OF), elevated plus maze (EPM) and radial arm maze (RAM) tests were conducted following a 15-day withdrawal period. The results showed alterations in exploratory behaviour in the OF in the MA and ETOH-MA groups, and anxiety-like effects in the EPM in all three drug treatment groups. All three drug groups exhibited reference memory deficits in the RAM, but only the combination treatment group displayed alterations in working memory. Both MA and ETOH-MA treatments increased the length of doublecortin (DCX)-void gaps in the dentate gyrus but only ETOH-MA treatment increased the number of such gaps. An increased number and length of DCX-void gaps correlated with decreased exploratory activity in the OF, and impaired working memory in the RAM was associated with an augmented number of gaps. These findings suggest that alterations in adult hippocampal neurogenesis are linked to the persistent cognitive and behavioural deficits produced by alcohol and MA exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced AMPA Receptor Activity Increases Operant Alcohol Self-administration and Cue-Induced Reinstatement

PubMed Central

Cannady, Reginald; Fisher, Kristen R.; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W.

2012-01-01

Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased AMPA receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pretreated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response-contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pretreatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pretreatment did not alter locomotor activity. AMPA receptor involvement was confirmed because DNQX (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pretreatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle treated-P-rats. These data suggest that enhanced glutamate activity at AMPA receptors may be key in facilitating alcohol consumption and seeking behavior which could

Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.

PubMed

Cannady, Reginald; Fisher, Kristen R; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W

2013-01-01

Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA) receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol-reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pre-treated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pre-treatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pre-treatment did not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7-dinitroquinoxaline-2,3-dione (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pre-treatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle-treated P-rats. These data suggest that enhanced glutamate activity at AMPA

Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats.

PubMed

Brolese, Giovana; Lunardi, Paula; Broetto, Núbia; Engelke, Douglas S; Lírio, Franciane; Batassini, Cristiane; Tramontina, Ana Carolina; Gonçalves, Carlos-Alberto

2014-08-01

Alcohol consumption by women during gestation has become increasingly common. Although it is widely accepted that exposure to high doses of ethanol has long-lasting detrimental effects on brain development, the case for moderate doses is underappreciated, and benchmark studies have demonstrated structural and behavioral defects associated with moderate prenatal alcohol exposure in humans and animal models. This study aimed to investigate the influence of in utero exposure to moderate levels of ethanol throughout pregnancy on learning/memory, anxiety parameters and neuroglial parameters in adolescent offspring. Female rats were exposed to an experimental protocol throughout gestation up to weaning. After mating, the dams were divided into three groups and treated with only water (control), non-alcoholic beer (vehicle) or 10% (vv) beer solution (moderate prenatal alcohol exposure - MPAE). Adolescent male offspring were subjected to the plus-maze discriminative avoidance task to evaluate learning/memory and anxiety-like behavior. Hippocampi were dissected and slices were obtained for immunoquantification of GFAP, NeuN, S100B and the NMDA receptor. The MPAE group clearly presented anxiolytic-like behavior, even though they had learned how to avoid the aversive arm. S100B protein was increased in the cerebrospinal fluid (CSF) in the group treated with alcohol, and alterations in GFAP expression were also shown. This study indicates that moderate ethanol doses administered during pregnancy could induce anxiolytic-like effects, suggesting an increase in risk-taking behavior in adolescent male offspring. Furthermore, the data show the possibility that glial cells are involved in the altered behavior present after prenatal ethanol treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis.

PubMed

Perkins, Amy E; Fadel, Jim R; Kelly, Sandra J

2015-05-01

Fetal alcohol spectrum disorders (FASD) are characterized by damage to multiple brain regions, including the hippocampus, which is involved in learning and memory. The acetylcholine neurotransmitter system provides major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intubation to male rat pups (postnatal day [PD] 2-10; ethanol-treated [ET]). Controls received a sham intubation (IC) or no treatment (NC). Acetylcholine efflux was measured using in vivo microdialysis (PD 32-35). ET animals were not different at baseline, but had decreased K(+)/Ca(2+)-induced acetylcholine efflux compared to NC animals and an enhanced acetylcholine response to galantamine (acetylcholinesterase inhibitor; 2.0 mg/kg) compared to both control groups. A separate cohort of animals was tested in the context pre-exposure facilitation effect task (CPFE; PD 30-32) following postnatal alcohol exposure and administration of galantamine (2.0 mg/kg; PD 11-30). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Using immunohistochemistry, we found that neither alcohol exposure nor behavioral testing significantly altered the density of vesicular acetylcholine transporter or alpha7 nicotinic acetylcholine receptor in the ventral hippocampus (CA1). In the medial septum, the average number of choline acetyltransferase (ChAT+) cells was increased in ET animals that displayed the context-shock association; there were no changes in IC and NC animals that learned the context-shock association or in any animals that were in the control task that entailed no learning. Taken together, these results indicate that the hippocampal acetylcholine system is significantly disrupted under conditions of pharmacological manipulations (e.g., galantamine) in alcohol-exposed animals. Furthermore, ChAT was up‑regulated in ET animals that learned the CPFE, which may account for their ability

Taste responses to monosodium glutamate after alcohol exposure.

PubMed

Wrobel, Elzbieta; Skrok-Wolska, Dominika; Ziolkowski, Marcin; Korkosz, Agnieszka; Habrat, Boguslaw; Woronowicz, Bohdan; Kukwa, Andrzej; Kostowski, Wojciech; Bienkowski, Przemyslaw; Scinska, Anna

2005-01-01

The aim of the present study was to evaluate the effects of acute and chronic exposure to alcohol on taste responses to a prototypic umami substance, monosodium glutamate (MSG). The rated intensity and pleasantness of MSG taste (0.03-10.0%) was compared in chronic male alcoholics (n = 35) and control subjects (n = 25). In a separate experiment, the effects of acute exposure of the oral mucosa to ethanol rinse (0.5-4.0%) on MSG taste (0.3-3.0%) were studied in 10 social drinkers. The alcoholic and control group did not differ in terms of the rated intensity and pleasantness of MSG taste. Electrogustometric thresholds were significantly (P < 0.01) higher, i.e. worse, in the alcohol-dependent subjects. The difference remained significant after controlling for between-group differences in cigarette smoking and coffee drinking. Rinsing with ethanol did not alter either intensity or pleasantness of MSG taste in social drinkers. The present results suggest that: (i) neither acute nor chronic alcohol exposure modifies taste responses to MSG; (ii) alcohol dependence may be associated with deficit in threshold taste reactivity, as assessed by electrogustometry.

Impact of alcohol advertising and media exposure on adolescent alcohol use: a systematic review of longitudinal studies.

PubMed

Anderson, Peter; de Bruijn, Avalon; Angus, Kathryn; Gordon, Ross; Hastings, Gerard

2009-01-01

To assess the impact of alcohol advertising and media exposure on future adolescent alcohol use. We searched MEDLINE, the Cochrane Library, Sociological Abstracts, and PsycLIT, from 1990 to September 2008, supplemented with searches of Google scholar, hand searches of key journals and reference lists of identified papers and key publications for more recent publications. We selected longitudinal studies that assessed individuals' exposure to commercial communications and media and alcohol drinking behaviour at baseline, and assessed alcohol drinking behaviour at follow-up. Participants were adolescents aged 18 years or younger or below the legal drinking age of the country of origin of the study, whichever was the higher. Thirteen longitudinal studies that followed up a total of over 38,000 young people met inclusion criteria. The studies measured exposure to advertising and promotion in a variety of ways, including estimates of the volume of media and advertising exposure, ownership of branded merchandise, recall and receptivity, and one study on expenditure on advertisements. Follow-up ranged from 8 to 96 months. One study reported outcomes at multiple time-points, 3, 5, and 8 years. Seven studies provided data on initiation of alcohol use amongst non-drinkers, three studies on maintenance and frequency of drinking amongst baseline drinkers, and seven studies on alcohol use of the total sample of non-drinkers and drinkers at baseline. Twelve of the thirteen studies concluded an impact of exposure on subsequent alcohol use, including initiation of drinking and heavier drinking amongst existing drinkers, with a dose response relationship in all studies that reported such exposure and analysis. There was variation in the strength of association, and the degree to which potential confounders were controlled for. The thirteenth study, which tested the impact of outdoor advertising placed near schools failed to detect an impact on alcohol use, but found an impact on

A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

PubMed

Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

2014-05-28

In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. Copyright © 2014 the authors 0270-6474/14/347447-11$15.00/0.

The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis

PubMed Central

Perkins, Amy E.; Fadel, Jim R.; Kelly, Sandra J.

2015-01-01

Fetal alcohol spectrum disorders (FASD) affect 2–5% of children. FASD have been shown to cause damage to multiple brain regions, but damage to the hippocampus specifically may explain deficits in learning and memory that are hallmark symptoms of FASD. The acetylcholine neurotransmitter system is a major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intragastric intubation to developing male rat pups (postnatal day [PD] 2–10; ethanol-treated [ET]), with controls receiving a sham intubation (IC) or no treatment (NC). In Experiment 1, in vivo microdialysis was used to measure acetylcholine efflux in adolescents (PD 32–35). During microdialysis, the effects of a high K+/Ca2+ aCSF solution (PD 32–33) and an acute galantamine (acetylcholinesterase [AChE] inhibitor) injection (2.0 mg/kg; PD 34–35) on acetylcholine efflux were measured. Alcohol-exposed animals did not differ in acetylcholine efflux at baseline. However, alcohol-exposed animals had a decrease in K+/Ca2+-induced acetylcholine efflux compared to non-treated controls, and an enhanced acetylcholine response to galantamine compared to both control groups. Experiment 2 tested whether chronic administration of galantamine (2.0 mg/kg; PD 11–30) could attenuate alcohol-induced learning deficits in the context pre-exposure facilitation effect (CPFE; PD 30–32). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Immunohistochemistry was used to measure expression of choline acetyltransferase (ChAT; medial septum), vesicular acetylcholine transporter (vAChT; ventral CA1), and the alpha7 nicotinic acetylcholine receptor (α7 nAChR; ventral CA1) following microdialysis (Exp. 1) or chronic galantamine and behavioral testing (Exp. 2). Neither alcohol exposure nor behavioral testing significantly altered the density of vAChT or α7 nAChRs in the ventral CA1 region of the

Role of Ventral Subiculum in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence

PubMed Central

Campbell, Erin J.; Whitaker, Leslie R.; Harvey, Brandon K.; Kaganovsky, Konstantin; Adhikary, Sweta; Hope, Bruce T.; Heins, Robert C.; Prisinzano, Thomas E.; Vardy, Eyal; Bonci, Antonello; Bossert, Jennifer M.

2016-01-01

In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol drinking. We recently developed a rat model of this human condition in which we train alcohol-preferring P rats to self-administer alcohol in one context (A), punish the alcohol-reinforced responding in a different context (B), and then test for relapse to alcohol seeking in Contexts A and B without alcohol or shock. Here, we studied the role of projections to nucleus accumbens (NAc) shell from ventral subiculum (vSub), basolateral amygdala, paraventricular thalamus, and ventral medial prefrontal cortex in context-induced relapse after punishment-imposed abstinence. First, we measured double-labeling of the neuronal activity marker Fos with the retrograde tracer cholera toxin subunit B (injected in NAc shell) and demonstrated that context-induced relapse is associated with selective activation of the vSub→NAc shell projection. Next, we reversibly inactivated the vSub with GABA receptor agonists (muscimol+baclofen) before the context-induced relapse tests and provided evidence for a causal role of vSub in this relapse. Finally, we used a dual-virus approach to restrict expression of the inhibitory κ opioid-receptor based DREADD (KORD) in vSub→NAc shell projection neurons. We found that systemic injections of the KORD agonist salvinorin B, which selectively inhibits KORD-expressing neurons, decreased context-induced relapse to alcohol seeking. Our results demonstrate a critical role of vSub in context-induced relapse after punishment-imposed abstinence and further suggest a role of the vSub→NAc projection in this relapse. SIGNIFICANCE STATEMENT In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol

Role of Ventral Subiculum in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence.

PubMed

Marchant, Nathan J; Campbell, Erin J; Whitaker, Leslie R; Harvey, Brandon K; Kaganovsky, Konstantin; Adhikary, Sweta; Hope, Bruce T; Heins, Robert C; Prisinzano, Thomas E; Vardy, Eyal; Bonci, Antonello; Bossert, Jennifer M; Shaham, Yavin

2016-03-16

In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol drinking. We recently developed a rat model of this human condition in which we train alcohol-preferring P rats to self-administer alcohol in one context (A), punish the alcohol-reinforced responding in a different context (B), and then test for relapse to alcohol seeking in Contexts A and B without alcohol or shock. Here, we studied the role of projections to nucleus accumbens (NAc) shell from ventral subiculum (vSub), basolateral amygdala, paraventricular thalamus, and ventral medial prefrontal cortex in context-induced relapse after punishment-imposed abstinence. First, we measured double-labeling of the neuronal activity marker Fos with the retrograde tracer cholera toxin subunit B (injected in NAc shell) and demonstrated that context-induced relapse is associated with selective activation of the vSub→NAc shell projection. Next, we reversibly inactivated the vSub with GABA receptor agonists (muscimol+baclofen) before the context-induced relapse tests and provided evidence for a causal role of vSub in this relapse. Finally, we used a dual-virus approach to restrict expression of the inhibitory κ opioid-receptor based DREADD (KORD) in vSub→NAc shell projection neurons. We found that systemic injections of the KORD agonist salvinorin B, which selectively inhibits KORD-expressing neurons, decreased context-induced relapse to alcohol seeking. Our results demonstrate a critical role of vSub in context-induced relapse after punishment-imposed abstinence and further suggest a role of the vSub→NAc projection in this relapse. In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol use. Until recently, an

Neurobehavioral Disorder Associated With Prenatal Alcohol Exposure

PubMed Central

Hagan, Joseph F.; Balachova, Tatiana; Bertrand, Jacquelyn; Chasnoff, Ira; Dang, Elizabeth; Fernandez-Baca, Daniel; Kable, Julie; Kosofsky, Barry; Senturias, Yasmin N.; Singh, Natasha; Sloane, Mark; Weitzman, Carol; Zubler, Jennifer

2017-01-01

Children and adolescents affected by prenatal exposure to alcohol who have brain damage that is manifested in functional impairments of neurocognition, self-regulation, and adaptive functioning may most appropriately be diagnosed with neurobehavioral disorder associated with prenatal exposure. This Special Article outlines clinical implications and guidelines for pediatric medical home clinicians to identify, diagnose, and refer children regarding neurobehavioral disorder associated with prenatal exposure. Emphasis is given to reported or observable behaviors that can be identified as part of care in pediatric medical homes, differential diagnosis, and potential comorbidities. In addition, brief guidance is provided on the management of affected children in the pediatric medical home. Finally, suggestions are given for obtaining prenatal history of in utero exposure to alcohol for the pediatric patient. PMID:27677572

Dose–response study of chronic alcohol induced changes in sleep patterns in rats

PubMed Central

Mukherjee, Sanjib; Kazerooni, Morvarid; Simasko, Steven M.

2008-01-01

The goal of the present study was to determine an optimum exposure regimen for alterations in sleep induced by chronic alcohol treatments in rats. We used two different exposure routes (alcohol in water and alcohol in liquid diet at two different doses in each regimen (6% and 12% alcohol in water and 3% and 6% alcohol in liquid diet)). All treatments were for 6 weeks. We found the effects of the 6% and 12% in water and 3% in liquid diet to be very similar; all three produced increases in slow-wave sleep (SWS) only in the dark period with no changes in rapid-eye-movement sleep (REMS). On the other hand 6% alcohol in liquid diet caused much more dramatic changes, with alterations in both SWS and REMS in both the dark and light periods. These animals spent less time in SWS and REMS during the light period but more time in SWS and REMS in the dark period. Additionally, the variation of slow-wave amplitude (SWA) across day and night in this group of alcoholic animals is blunted with the loss of the peak of SWA at the beginning of light onset compared to the other groups. We conclude that future alcohol treatment regimens used to investigate the effects of alcohol on sleep in adult rats should use an exposure protocol of at least 6 weeks with 6% alcohol in liquid diet. PMID:18387599

Amount of Televised Alcohol Advertising Exposure and the Quantity of Alcohol Consumed by Youth.

PubMed

Naimi, Timothy S; Ross, Craig S; Siegel, Michael B; DeJong, William; Jernigan, David H

2016-09-01

Although studies demonstrate that exposure to brand-specific alcohol advertising is associated with an increased likelihood of youth consuming particular brands, the relationship between quantity of brand-specific advertising exposure and quantity of brand-specific consumption has not been firmly established. Using the Alcohol Brand Research Among Underage Drinkers (ABRAND) national sample of 1,031 young drinkers (ages 13-20), this study examined the relationship between their aggregated past-year exposure to advertising (in adstock units, a measure based on gross rating points) for 61 alcohol brands that advertised on the 20 most popular nonsports television programs viewed by underage youth and their aggregated total consumption of those same brands during the past 30 days. Predictive models adjusted for other media exposure, predictors of youth's alcohol consumption, and the consumption of brands not advertised on the 20 shows. For the fully adjusted models, each 100 adstock unit increase in exposure (about 1 SD) was associated with an increase of 5.9 drinks (95% CI [0.9, 11.0 drinks]) consumed during the past 30 days among those with less than 300 units of advertising exposure, and an increase of 55.7 drinks (95% CI [13.9, 97.4 drinks]) among those with 300 or more adstock units of exposure. Among underage youth, the quantity of brand-specific advertising exposure is positively associated with the total quantity of consumption of those advertised brands, even after controlling for the consumption of non-advertised brands. Future research should examine exposure-consumption relationships longitudinally and in other media.

Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

PubMed

Bahi, Amine

2013-07-01

Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

2017-02-01

Nearly 2 million women in the United States alone are at risk for an alcohol-exposed pregnancy, including more than 600,000 who binge drink. Even low levels of prenatal alcohol exposure (PAE) can lead to a variety of birth defects, including craniofacial and neurodevelopmental defects, as well as increased risk of miscarriages and stillbirths. Studies have also shown an interaction between drinking while pregnant and an increase in congenital heart defects (CHD), including atrioventricular septal defects and other malformations. We have previously established a quail model of PAE, modeling a single binge drinking episode in the third week of a woman's pregnancy. Using optical coherence tomography (OCT), we quantified intraventricular septum thickness, great vessel diameters, and atrioventricular valve volumes. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septum, and aortic vessels. We previously showed that supplementation with the methyl donor betaine reduced gross defects, improved survival rates, and prevented cardiac defects. Here we show that these preventative effects are also observed with folate (another methyl donor) supplementation. Folate also appears to normalize retrograde flow levels which are elevated by ethanol exposure. Finally, preliminary findings have shown that glutathione, a crucial antioxidant, is noticeably effective at improving survival rates and minimizing gross defects in ethanol-exposed embryos. Current investigations will examine the impact of glutathione supplementation on PAE-related CHDs.

In Utero Alcohol Exposure, Epigenetic Changes, and Their Consequences

PubMed Central

Ungerer, Michelle; Knezovich, Jaysen; Ramsay, Michele

2013-01-01

Exposure to alcohol has serious consequences for the developing fetus, leading to a range of conditions collectively known as fetal alcohol spectrum disorders (FASD). Most importantly, alcohol exposure affects the development of the brain during critical periods of differentiation and growth, leading to cognitive and behavioral deficits. The molecular mechanisms and processes underlying the teratogenic effects of alcohol exposure remain poorly understood and are complex, because the specific effects depend on the timing, amount, and duration of exposure as well as genetic susceptibility. Accumulating evidence from studies on DNA methylation and histone modification that affect chromatin structure, as well as on the role of microRNAs in regulating mRNA levels supports the contribution of epigenetic mechanisms to the development of FASD. These epigenetic effects are difficult to study, however, because they often are cell-type specific and transient in nature. Rodent models play an important role in FASD research. Although recent studies using these models have yielded some insight into epigenetic mechanisms affecting brain development, they have generated more questions than they have provided definitive answers. Researchers are just beginning to explore the intertwined roles of different epigenetic mechanisms in neurogenesis and how this process is affected by exposure to alcohol, causing FASD. PMID:24313163

Behavioral deficits induced by third-trimester equivalent alcohol exposure in male C57BL/6J mice are not associated with reduced adult hippocampal neurogenesis but are still rescued with voluntary exercise.

PubMed

Hamilton, G F; Bucko, P J; Miller, D S; DeAngelis, R S; Krebs, C P; Rhodes, J S

2016-11-01

Prenatal alcohol exposure can produce permanent alterations in brain structure and profound behavioral deficits. Mouse models can help discover mechanisms and identify potentially useful interventions. This study examined long-term influences of either a single or repeated alcohol exposure during the third-trimester equivalent on survival of new neurons in the hippocampus, behavioral performance on the Passive avoidance and Rotarod tasks, and the potential role of exercise as a therapeutic intervention. C57BL/6J male mice received either saline or 5g/kg ethanol split into two s.c. injections, two hours apart, on postnatal day (PD)7 (Experiment 1) or on PD5, 7 and 9 (Experiment 2). All mice were weaned on PD21 and received either a running wheel or remained sedentary from PD35-PD80/81. From PD36-45, mice received i.p. injections of 50mg/kg bromodeoxyuridine (BrdU) to label dividing cells. Behavioral testing occurred between PD72-79. Number of surviving BrdU+ cells and immature neurons (doublecortin; DCX+) was measured at PD80-81. Alcohol did not affect number of BrdU+ or DCX+ cells in either experiment. Running significantly increased number of BrdU+ and DCX+ cells in both treatment groups. Alcohol-induced deficits on Rotarod performance and acquisition of the Passive avoidance task (Day 1) were evident only in Experiment 2 and running rescued these deficits. These data suggest neonatal alcohol exposure does not result in long-term impairments in adult hippocampal neurogenesis in the mouse model. Three doses of ethanol were necessary to induce behavioral deficits. Finally, the mechanisms by which exercise ameliorated the neonatal alcohol induced behavioral deficits remain unknown. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wahlang, Banrida; Song, Ming; Beier, Juliane I.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposuremore » was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg

Watching and drinking: expectancies, prototypes, and friends' alcohol use mediate the effect of exposure to alcohol use in movies on adolescent drinking.

PubMed

Dal Cin, Sonya; Worth, Keilah A; Gerrard, Meg; Stoolmiller, Mike; Sargent, James D; Wills, Thomas A; Gibbons, Frederick X

2009-07-01

To investigate the psychological processes that underlie the relation between exposure to alcohol use in media and adolescent alcohol use. The design consisted of a structural equation modeling analysis of data from four waves of a longitudinal, nationally representative, random-digit dial telephone survey of adolescents in the United States. The main outcome measures were adolescent alcohol consumption and willingness to use alcohol. Tested mediators were alcohol-related norms, prototypes, expectancies, and friends' use. Alcohol prototypes, expectancies, willingness, and friends' use of alcohol (but not perceived prevalence of alcohol use among peers) were significant mediators of the relation between movie alcohol exposure and alcohol consumption, even after controlling for demographic, child, and family factors associated with both movie exposure and alcohol consumption. Established psychological and interpersonal predictors of alcohol use mediate the effects of exposure to alcohol use in movies on adolescent alcohol consumption. The findings suggest that exposure to movie portrayals may operate through similar processes as other social influences, highlighting the importance of considering these exposures in research on adolescent risk behavior.

Alcohol Exposure after Mild Focal Traumatic Brain Injury Impairs Neurological Recovery and Exacerbates Localized Neuroinflammation

PubMed Central

Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

2014-01-01

Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (~300 g) were subjected to a mild focal TBI by lateral fluid percussion (~30 PSI, ~25 ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on /10h off; BAL~200 mg/dL) or room air for 10 days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation. PMID:25489880

Subjective aggression during alcohol and cannabis intoxication before and after aggression exposure.

PubMed

De Sousa Fernandes Perna, E B; Theunissen, E L; Kuypers, K P C; Toennes, S W; Ramaekers, J G

2016-09-01

Alcohol and cannabis use have been implicated in aggression. Alcohol consumption is known to facilitate aggression, whereas a causal link between cannabis and aggression has not been clearly demonstrated. This study investigated the acute effects of alcohol and cannabis on subjective aggression in alcohol and cannabis users, respectively, following aggression exposure. Drug-free controls served as a reference. It was hypothesized that aggression exposure would increase subjective aggression in alcohol users during alcohol intoxication, whereas it was expected to decrease subjective aggression in cannabis users during cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21), and controls (n = 20) were included in a mixed factorial study. Alcohol and cannabis users received single doses of alcohol and placebo or cannabis and placebo, respectively. Subjective aggression was assessed before and after aggression exposure consisting of administrations of the point-subtraction aggression paradigm (PSAP) and the single category implicit association test (SC-IAT). Testosterone and cortisol levels in response to alcohol/cannabis treatment and aggression exposure were recorded as secondary outcome measures. Subjective aggression significantly increased following aggression exposure in all groups while being sober. Alcohol intoxication increased subjective aggression whereas cannabis decreased the subjective aggression following aggression exposure. Aggressive responses during the PSAP increased following alcohol and decreased following cannabis relative to placebo. Changes in aggressive feeling or response were not correlated to the neuroendocrine response to treatments. It is concluded that alcohol facilitates feelings of aggression whereas cannabis diminishes aggressive feelings in heavy alcohol and regular cannabis users, respectively.

Dynamic Exposure to Alcohol Advertising in a Sports Context Influences Implicit Attitudes.

PubMed

Zerhouni, Oulmann; Bègue, Laurent; Duke, Aaron A; Flaudias, Valentin

2016-02-01

Experimental studies investigating the impact of advertising with ecological stimuli on alcohol-related cognition are scarce. This research investigated the cognitive processes involved in learning implicit attitudes toward alcohol after incidental exposure to alcohol advertisements presented in a dynamic context. We hypothesized that incidental exposure to a specific alcohol brand would lead to heightened positive implicit attitudes toward alcohol due to a mere exposure effect. In total, 108 participants were randomly exposed to dynamic sporting events excerpts with and without advertising for a specific brand of alcohol, after completing self-reported measures of alcohol-related expectancies, alcohol consumption, and attitudes toward sport. Participants then completed a lexical decision task and an affective priming task. We showed that participants were faster to detect brand name after being exposed to advertising during a sports game, and that implicit attitudes of participants toward the brand were more positive after they were exposed to advertising, even when alcohol usage patterns were controlled for. Incidental exposure to alcohol sponsorship in sport events impacts implicit attitudes toward the advertised brand and alcohol in general. The effect of incidental advertising on implicit attitudes is also likely to be due to a mere exposure effect. However, further studies should address this point specifically. Copyright © 2016 by the Research Society on Alcoholism.

Human Brain Abnormalities Associated With Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder

PubMed Central

Jarmasz, Jessica S.; Basalah, Duaa A.; Chudley, Albert E.; Del Bigio, Marc R.

2017-01-01

Abstract Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental problem, but neuropathologic descriptions are rare and focused on the extreme abnormalities. We conducted a retrospective survey (1980–2016) of autopsies on 174 individuals with prenatal alcohol exposure or an FASD diagnosis. Epidemiologic details and neuropathologic findings were categorized into 5 age groups. Alcohol exposure was difficult to quantify. When documented, almost all mothers smoked tobacco, many abused other substances, and prenatal care was poor or nonexistent. Placental abnormalities were common (68%) in fetal cases. We identified micrencephaly (brain weight <5th percentile) in 31, neural tube defects in 5, isolated hydrocephalus in 6, corpus callosum defects in 6 (including some with complex anomalies), probable prenatal ischemic lesions in 5 (excluding complications of prematurity), minor subarachnoid heterotopias in 4, holoprosencephaly in 1, lissencephaly in 1, and cardiac anomalies in 26 cases. The brain abnormalities associated with prenatal alcohol exposure are varied; cause–effect relationships cannot be determined. FASD is likely not a monotoxic disorder. The animal experimental literature, which emphasizes controlled exposure to ethanol alone, is therefore inadequate. Prevention must be the main societal goal, however, a clear understanding of the neuropathology is necessary for provision of care to individuals already affected. PMID:28859338

Amount of Televised Alcohol Advertising Exposure and the Quantity of Alcohol Consumed by Youth

PubMed Central

Naimi, Timothy S.; Ross, Craig S.; Siegel, Michael B.; DeJong, William; Jernigan, David H.

2016-01-01

Objective: Although studies demonstrate that exposure to brand-specific alcohol advertising is associated with an increased likelihood of youth consuming particular brands, the relationship between quantity of brand-specific advertising exposure and quantity of brand-specific consumption has not been firmly established. Method: Using the Alcohol Brand Research Among Underage Drinkers (ABRAND) national sample of 1,031 young drinkers (ages 13–20), this study examined the relationship between their aggregated past-year exposure to advertising (in adstock units, a measure based on gross rating points) for 61 alcohol brands that advertised on the 20 most popular nonsports television programs viewed by underage youth and their aggregated total consumption of those same brands during the past 30 days. Predictive models adjusted for other media exposure, predictors of youth’s alcohol consumption, and the consumption of brands not advertised on the 20 shows. Results: For the fully adjusted models, each 100 adstock unit increase in exposure (about 1 SD) was associated with an increase of 5.9 drinks (95% CI [0.9, 11.0 drinks]) consumed during the past 30 days among those with less than 300 units of advertising exposure, and an increase of 55.7 drinks (95% CI [13.9, 97.4 drinks]) among those with 300 or more adstock units of exposure. Conclusions: Among underage youth, the quantity of brand-specific advertising exposure is positively associated with the total quantity of consumption of those advertised brands, even after controlling for the consumption of non-advertised brands. Future research should examine exposure–consumption relationships longitudinally and in other media. PMID:27588530

Chronic Alcohol Induces M2 Polarization Enhancing Pulmonary Disease Caused by Exposure to Particulate Air Pollution

PubMed Central

Thevenot, Paul; Saravia, Jordy; Giaimo, Joseph; Happel, Kyle I.; Dugas, Tammy R.; Cormier, Stephania A.

2013-01-01

Background Chronic alcohol consumption causes persistent oxidative stress in the lung, leading to impaired alveolar macrophage (AM) function and impaired immune responses. AMs play a critical role in protecting the lung from particulate matter (PM) inhalation by removing particulates from the airway and secreting factors which mediate airway repair. We hypothesized AM dysfunction caused by chronic alcohol consumption increases the severity of injury caused by particulate matter inhalation. Methods Age- and sex-matched C57BL6 mice were fed the Lieber-DeCarli liquid diet containing either alcohol or an iso-caloric substitution (control diet) for 8 weeks. Mice from both diet groups were exposed to combustion derived PM (CDPM) for the final 2 weeks. AM number, maturation, and polarization status were assessed by flow cytometry. Noninvasive and invasive strategies were used to assess pulmonary function and correlated with histomorphological assessments of airway structure and matrix deposition. Results Co-exposure to alcohol and CDPM decreased AM number and maturation status (CD11c expression) while increasing markers of M2 activation (IL-4Rα, Ym1, Fizz1 expression and IL-10 and TGF-β production). Changes in AM function were accompanied by decreased airway compliance and increased elastance. Altered lung function was attributable to elevated collagen content localized to the small airways and loss of alveolar integrity. Intranasal administration of neutralizing antibody to TGF-β during the CDPM exposure period improved changes in airway compliance and elastance while reducing collagen content caused by co-exposure. Conclusion CDPM inhalation causes enhanced disease severity in the alcoholic lung by stimulating the release of latent TGF-β stores in AMs. The combinatorial effect of elevated TGF-β, M2 polarization of AMs, and increased oxidative stress impairs pulmonary function by increasing airway collagen content and compromising alveolar integrity. PMID:23763452

Effects of alcohol advertising exposure on drinking among youth.

PubMed

Snyder, Leslie B; Milici, Frances Fleming; Slater, Michael; Sun, Helen; Strizhakova, Yuliya

2006-01-01

To test whether alcohol advertising expenditures and the degree of exposure to alcohol advertisements affect alcohol consumption by youth. Longitudinal panel using telephone surveys. Households in 24 US media markets, April 1999 to February 2001. Individuals aged 15 to 26 years were randomly sampled within households and households within media markets. Markets were systematically selected from the top 75 media markets, representing 79% of the US population. The baseline refusal rate was 24%. Sample sizes per wave were 1872, 1173, 787, and 588. Data on alcohol advertising expenditures on television, radio, billboards, and newspapers were collected. Market alcohol advertising expenditures per capita and self-reported alcohol advertising exposure in the prior month. Self-reported number of alcoholic drinks consumed in the prior month. Youth who saw more alcohol advertisements on average drank more (each additional advertisement seen increased the number of drinks consumed by 1% [event rate ratio, 1.01; 95% confidence interval, 1.01-1.02]). Youth in markets with greater alcohol advertising expenditures drank more (each additional dollar spent per capita raised the number of drinks consumed by 3% [event rate ratio, 1.03; 95% confidence interval, 1.01-1.05]). Examining only youth younger than the legal drinking age of 21 years, alcohol advertisement exposure and expenditures still related to drinking. Youth in markets with more alcohol advertisements showed increases in drinking levels into their late 20s, but drinking plateaued in the early 20s for youth in markets with fewer advertisements. Control variables included age, gender, ethnicity, high school or college enrollment, and alcohol sales. Alcohol advertising contributes to increased drinking among youth.

Alteration of gene expression by alcohol exposure at early neurulation.

PubMed

Zhou, Feng C; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R; Liang, Tiebing; McClintick, Jeanette N; Edenberg, Howard J; Li, Lang

2011-02-21

We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube

Chronic alcohol feeding potentiates hormone‐induced calcium signalling in hepatocytes

PubMed Central

Bartlett, Paula J.; Antony, Anil Noronha; Agarwal, Amit; Hilly, Mauricette; Prince, Victoria L.; Combettes, Laurent; Hoek, Jan B.

2017-01-01

Key points Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined.We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca2+‐mobilizing hormones resulting in a leftward shift in the concentration–response relationship and the transition from oscillatory to more sustained and prolonged Ca2+ increases.Our data demonstrate that alcohol‐dependent adaptation in the Ca2+ signalling pathway occurs at the level of hormone‐induced inositol 1,4,5 trisphosphate (IP3) production and does not involve changes in the sensitivity of the IP3 receptor or size of internal Ca2+ stores.We suggest that prolonged and aberrant hormone‐evoked Ca2+ increases may stimulate the production of mitochondrial reactive oxygen species and contribute to alcohol‐induced hepatocyte injury. Abstract ‘Adaptive’ responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide‐dependent cytosolic calcium ([Ca2+]i) increases, which can adversely affect mitochondrial Ca2+ levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose–response for Ca2+‐mobilizing hormones resulting in more sustained and prolonged [Ca2+]i increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca2+ increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. Acute alcohol treatment (25 mm) completely inhibited hormone‐induced calcium increases in control livers, but not after chronic alcohol‐feeding, suggesting desensitization to the inhibitory actions of ethanol. Hormone‐induced inositol 1,4,5 trisphosphate (IP3) accumulation and

Alcohol-induced versus anion-induced states of alpha-chymotrypsinogen A at low pH.

PubMed

Khan, F; Khan, R H; Muzammil, S

2000-09-29

Characterization of conformational transition and folding intermediates is central to the study of protein folding. We studied the effect of various alcohols (trifluoroethanol (TFE), butanol, propanol, ethanol and methanol) and salts (K(3)FeCN(6), Na(2)SO(4), KClO(4) and KCl) on the acid-induced state of alpha-chymotrypsinogen A, a predominantly beta-sheet protein, at pH 2.0 by near-UV circular dichroism (CD), far-UV CD and 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence measurements. Addition of alcohols led to an increase in ellipticity value at 222 nm indicating the formation of alpha-helical structure. The order of effectiveness of alcohols was shown to be TFE>butanol>propanol>ethanol>methanol. ANS fluorescence data showed a decrease in fluorescence intensity on alcohol addition, suggesting burial of hydrophobic patches. The near-UV CD spectra showed disruption of tertiary structure on alcohol addition. No change in ellipticity was observed on addition of salts at pH 2.0, whereas in the presence of 2 M urea, salts were found to induce a molten globule-like state as evident from the increases in ellipticity at 222 nm and ANS fluorescence indicating exposure of hydrophobic regions of the protein. The effectiveness in inducing the molten globule-like state, i.e. both increase in ellipticity at 222 nm and increase in ANS fluorescence, followed the order K(3)FeCN(6)>Na(2)SO(4)>KClO(4)>KCl. The loss of signal in the near-UV CD spectrum on addition of alcohols indicating disordering of tertiary structure results suggested that the decrease in ANS fluorescence intensity may be attributed to the unfolding of the ANS binding sites. The results imply that the alcohol-induced state had characteristics of an unfolded structure and lies between the molten globule and the unfolded state. Characterization of such partially folded states has important implications for protein folding.

Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial

PubMed Central

Pittler, Max H.; White, Adrian R.; Stevinson, Clare; Ernst, Edzard

2003-01-01

Background Extract of globe artichoke (Cynara scolymus) is promoted as a possible preventive or cure for alcohol-induced hangover symptoms. However, few rigorous clinical trials have assessed the effects of artichoke extract, and none has examined the effects in relation to hangovers. We undertook this study to test whether artichoke extract is effective in preventing the signs and symptoms of alcohol-induced hangover. Methods We recruited healthy adult volunteers between 18 and 65 years of age to participate in a randomized double-blind crossover trial. Participants received either 3 capsules of commercially available standardized artichoke extract or indistinguishable, inert placebo capsules immediately before and after alcohol exposure. After a 1-week washout period the volunteers received the opposite treatment. Participants predefined the type and amount of alcoholic beverage that would give them a hangover and ate the same meal before commencing alcohol consumption on the 2 study days. The primary outcome measure was the difference in hangover severity scores between the artichoke extract and placebo interventions. Secondary outcome measures were differences between the interventions in scores using a mood profile questionnaire and cognitive performance tests administered 1 hour before and 10 hours after alcohol exposure. Results Fifteen volunteers participated in the study. The mean number (and standard deviation) of alcohol units (each unit being 7.9 g, or 10 mL, of ethanol) consumed during treatment with artichoke extract and placebo was 10.7 (3.1) and 10.5 (2.4) respectively, equivalent to 1.2 (0.3) and 1.2 (0.2) g of alcohol per kilogram body weight. The volume of nonalcoholic drink consumed and the duration of sleep were similar during the artichoke extract and placebo interventions. None of the outcome measures differed significantly between interventions. Adverse events were rare and were mild and transient. Interpretation Our results suggest that

Autophagy in alcohol-induced liver diseases

PubMed Central

Dolganiuc, Angela; Thomes, Paul G.; Ding, Wen-Xing; Lemasters, John J.; Donohue, Terrence M.

2013-01-01

Alcohol is the most abused substance worldwide and a significant source of liver injury; the mechanisms of alcohol-induced liver disease are not fully understood. Significant cellular toxicity and impairment of protein synthesis and degradation occur in alcohol-exposed liver cells, along with changes in energy balance and modified responses to pathogens. Autophagy is the process of cellular catabolism through the lysosomal-dependent machinery, which maintains a balance among protein synthesis, degradation, and recycling of self. Autophagy is part of normal homeostasis and it can be triggered by multiple factors that threaten cell integrity including starvation, toxins, or pathogens. Multiple factors regulate autophagy; survival and preservation of cellular integrity at the expense of inadequately-folded proteins and damaged high energy-generating intracellular organelles are prominent targets of autophagy in pathologic conditions. Coincidentally, inadequately-folded proteins accumulate and high energy-generating intracellular organelles, such as mitochondria, are damaged by alcohol abuse; these alcohol-induced pathological findings prompted investigation of the role of autophagy in the pathogenesis of alcohol-induced liver damage. Our review summarizes the current knowledge about the role and implications of autophagy in alcohol-induced liver disease. PMID:22551004

Exposure to alcohol use in motion pictures and teen drinking in Germany.

PubMed

Hanewinkel, Reiner; Tanski, Susanne E; Sargent, James D

2007-10-01

To assess whether movie alcohol exposure is associated with alcohol use during early adolescence. We conducted a survey of adolescents (N = 5,581) from 27 schools in Germany. Each was asked if he/she had seen a list of 50 movie titles, randomly selected from a sample of 398 US box office hits released there. Screen alcohol use was timed for each movie, summed for movies each adolescent had seen, and adjusted to reflect exposure to all 398 movies. We assessed the association between this exposure and any alcohol use without parental knowledge (WPK) and binge drinking (>or= 5 drinks). Alcohol use was depicted in 88% of the 398 movies. Median exposure to movie alcohol use was 3.44 h (interquartile range = 1.51-6.23 h). Overall 36.6% of subjects used alcohol WPK and 18.1% reported binge drinking. Movie alcohol exposure was directly associated with alcohol use WPK and binge drinking, after controlling for multiple covariates including sociodemographics, personality characteristics and social influences. Compared with quartile one, the adjusted odds of alcohol use WPK were 1.47 [95% confidence interval (CI) 1.19-1.82], 2.12 (1.75-2.57) and 2.95 (2.35-3.70) for quartiles 2, 3 and 4, respectively; similarly, adjusted odds of binge drinking were 1.42 (0.93-2.28), 1.84 (1.27-2.67) and 2.59 (1.70-3.95). This study demonstrates an association between exposure to alcohol use in US movies and alcohol use without parental knowledge in Germany, and is the first study to link movie exposure with binge drinking. Given international distribution of US movies, depicted behaviours may influence adolescents outside the country of origin.

Differentiating the Effects of Familial Risk for Alcohol Dependence and Prenatal Exposure to Alcohol on Offspring Brain Morphology.

PubMed

Sharma, Vinod K; Hill, Shirley Y

2017-02-01

Offspring with a family history of alcohol dependence (AD) have been shown to have altered structural and functional integrity of corticolimbic brain structures. Similarly, prenatal exposure to alcohol is associated with a variety of structural and functional brain changes. The goal of this study was to differentiate the brain gray matter volumetric differences associated with familial risk and prenatal exposure to alcohol among offspring while controlling for lifetime personal exposures to alcohol and drugs. A total of 52 high-risk (HR) offspring from maternal multiplex families with a high proportion of AD were studied along with 55 low-risk (LR) offspring. Voxel-based morphometric analysis was performed using statistical parametric mapping (SPM8) software using 3T structural images from these offspring to identify gray matter volume differences associated with familial risk and prenatal exposure. Significant familial risk group differences were seen with HR males showing reduced volume of the left inferior temporal, left fusiform, and left and right insula regions relative to LR males, controlling for prenatal exposure to alcohol drugs and cigarettes. HR females showed a reduction in the right fusiform but also showed a reduction in volume in portions of the cerebellum (left crus I and left lobe 8). Prenatal alcohol exposure effects, assessed within the familial HR group, was associated with reduced right middle cingulum and left middle temporal volume. Even low exposure resulting from mothers drinking in amounts less than the median of those who drank (53 drinks or less over the course of the pregnancy) showed a reduction in volume in the right anterior cingulum and in the left cerebellum (lobes 4 and 5). Familial risk for AD and prenatal exposure to alcohol and other drugs show independent effects on brain morphology. Copyright © 2017 by the Research Society on Alcoholism.

Alcohol Activates the Hedgehog Pathway and Induces Related Pro-carcinogenic Processes in the Alcohol-Preferring Rat Model of Hepatocarcinogenesis

PubMed Central

Chan, Isaac S.; Guy, Cynthia D.; Machado, Mariana V.; Wank, Abigail; Kadiyala, Vishnu; Michelotti, Gregory; Choi, Steve; Swiderska-Syn, Marzena; Karaca, Gamze; Pereira, Thiago A.; Yip-Schneider, Michele T.; Schmidt, C. Max; Diehl, Anna Mae

2014-01-01

Background Alcohol consumption promotes hepatocellular carcinoma (HCC). The responsible mechanisms are not well understood. Hepatocarcinogenesis increases with age and is enhanced by factors that impose a demand for liver regeneration. Because alcohol is hepatotoxic, habitual alcohol ingestion evokes a recurrent demand for hepatic regeneration. The alcohol-preferring (P) rat model mimics the level of alcohol consumption by humans who habitually abuse alcohol. Previously, we showed that habitual heavy alcohol ingestion amplified age-related hepatocarcinogenesis in P-rats, with over 80% of alcohol-consuming P rats developing HCCs after 18 months of alcohol exposure, compared to only 5% of water-drinking controls. Methods Herein, we used quantitative real time PCR and quantitative immunocytochemistry to compare liver tissues from alcohol-consuming P rats and water-fed P rat controls after 6, 12, or 18 months of drinking. We aimed to identify potential mechanisms that might underlie the differences in liver cancer formation, and hypothesized that chronic alcohol ingestion would activate Hedgehog (HH), a regenerative signaling pathway that is over-activated in HCC. Results Chronic alcohol ingestion amplified age-related degenerative changes in hepatocytes, but did not cause appreciable liver inflammation or fibrosis even after 18 months of heavy drinking. HH signaling was also enhanced by alcohol exposure, as evidenced by increased levels of mRNAs encoding HH ligands, HH-regulated transcription factors, and HH-target genes. Immunocytochemistry confirmed increased alcohol-related accumulation of HH ligand-producing cells and HH-responsive target cells. HH-related regenerative responses were also induced in alcohol-exposed rats. Three of these processes (i.e., deregulated progenitor expansion, the reverse-Warburg effect, and epithelial-to-mesenchymal transitions) are known to promote cancer growth in other tissues. Conclusions Alcohol-related changes in Hedgehog signaling

Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes.

PubMed

Ray, Lara A

2011-01-01

Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress-induced and cue-induced craving in heavy drinkers by testing single-nucleotide polymorphisms (SNPs) of the corticotrophin-releasing hormone binding protein (CRH-BP) gene and the mu-opioid receptor (OPRM1) gene. This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non-treatment-seeking heavy drinkers. Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. These initial results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes. Human laboratory models of stress and cue-induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples. Copyright © 2010 by the Research Society on Alcoholism.

Brief and Extended Alcohol Cue Exposure Effects on Craving and Attentional Bias

PubMed Central

Ramirez, Jason J.; Monti, Peter M.; Colwill, Ruth M.

2015-01-01

Past research has shown that underage college student drinkers (UCSDs) report increased subjective craving and exhibit stronger attentional biases to alcohol following alcohol cue exposure. To date, less research has examined whether momentary decreases in alcohol craving are associated with reductions in attentional bias. One experimental manipulation that has been used to produce within-session decreases in alcohol craving is to extend the duration of laboratory-based alcohol cue exposure protocols. The aim of this study was to examine the effects of both brief and extended alcohol cue exposure on subjective craving and attentional bias among UCSDs. Eighty participants were randomized either to a group that received a short in vivo alcohol cue exposure period (Group Short Exposure [SE], two 3-min blocks) or to a group that received a long exposure period (Group Long Exposure [LE], six 3-min blocks). Both groups completed a visual probe task before and after cue exposure to assess changes in attentional bias. Analyses revealed no group differences in mean craving or mean attentional bias before or after cue exposure. Further, exploratory analyses revealed no sex differences in our measures of craving or attentional bias. For Group LE, but not Group SE, within-session changes in craving positively predicted within-session changes in attentional bias. However, further analyses revealed that this relationship was significant only for female participants in the LE Group. Implications for treatments that aim to reduce craving or attentional bias are discussed. PMID:26053323

Longitudinal study of exposure to entertainment media and alcohol use among german adolescents.

PubMed

Hanewinkel, Reiner; Sargent, James D

2009-03-01

Entertainment media exposure may predict teenager alcohol use, but few longitudinal studies have been reported. A longitudinal study was conducted of 2708 German adolescents aged 10 to 16 years who had never drunk alcohol. Each adolescent was surveyed at school about daily television use, whether they had a television in their bedroom, and their exposure to movie alcohol depictions. Adolescents were resurveyed 12 to 13 months later (retention rate: 85%) to determine onset of drinking alcohol without parental knowledge and binge drinking (>/=5 consecutive drinks). Overall, 885 (33%) students initiated alcohol use without parental knowledge (17% in quartile 1 movie alcohol exposure), and 387 (14%) initiated binge drinking during follow-up. After controlling for baseline covariates, exposure to movie alcohol use significantly increased percent initiating alcohol use (to 24% in exposure quartile 2, 33% in quartile 3 and 34% in quartile 4) and percent initiating binge drinking (to 8.6% in exposure quartile 2, 12% in quartile 3 and 13% in quartile 4). Having a television in the bedroom also predicted both outcomes, but daily television use did not. Movie exposure and having a television in the bedroom are both independent predictors of onset of problematic alcohol use among German teenagers. Media restrictions could play a role in prevention.

Exposure to alcohol advertising and adolescents' drinking beliefs: Role of message interpretation.

PubMed

Collins, Rebecca L; Martino, Steven C; Kovalchik, Stephanie A; D'Amico, Elizabeth J; Shadel, William G; Becker, Kirsten M; Tolpadi, Anagha

2017-09-01

Recent research revealed momentary associations between exposure to alcohol advertising and positive beliefs about alcohol among adolescents (Martino et al., 2016). We reanalyzed those data to determine whether associations depend on adolescents' appraisal of ads. Over a 10-month period in 2013, 589 youth, ages 11-14, in the Los Angeles, CA, area, participated in a 14-day ecological momentary assessment, logging all exposures to alcohol advertisements as they occurred and completing brief assessments of their skepticism toward, liking of, and identification with any people in each ad, as well as their alcohol-related beliefs at the moment. Participants also completed measures of their alcohol- related beliefs at random moments of nonexposure throughout each day. Mixed-effects regression models compared beliefs about alcohol at moments of exposure to alcohol advertising that was appraised in a particular way (e.g., with liking, without liking) to beliefs at random moments. When youth encountered ads they appraised positively, their beliefs about alcohol were significantly more positive than when they were queried at random moments. Beliefs in the presence of ads that were not positively appraised were generally similar to beliefs at random moments. Youth are active participants in the advertising process. How they respond to and process alcohol advertising strongly moderates the association between exposure and alcohol-related beliefs. More effort is needed to identify attributes of alcohol advertisements, and of youth, that determine how youth process alcohol ads. This information can be used to either limit exposure to problematic ads or make youth more resilient to such exposure. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Acute alcohol intoxication-induced microvascular leakage.

PubMed

Doggett, Travis M; Breslin, Jerome W

2014-09-01

Alcohol intoxication can increase inflammation and worsen injury, yet the mechanisms involved are not clear. We investigated whether acute alcohol intoxication increases microvascular permeability and investigated potential signaling mechanisms in endothelial cells that may be involved. Conscious rats received a 2.5 g/kg alcohol bolus via gastric catheters to produce acute intoxication. Microvascular leakage of intravenously administered fluorescein isothiocyanate (FITC)-conjugated albumin (FITC-albumin) from the mesenteric microcirculation was assessed by intravital microscopy. Endothelial-specific mechanisms were studied using cultured endothelial cell monolayers. Transendothelial electrical resistance (TER) served as an index of barrier function, before and after treatment with alcohol or its metabolite acetaldehyde. Pharmacologic agents were used to test the roles of alcohol metabolism, oxidative stress, p38 mitogen-activated protein kinase (MAPK), myosin light-chain kinase (MLCK), rho kinase (ROCK), and exchange protein activated by cAMP (Epac). VE-cadherin localization was investigated to assess junctional integrity. Rac1 and RhoA activation was assessed by ELISA assays. Alcohol significantly increased FITC-albumin extravasation from the mesenteric microcirculation. Alcohol also significantly decreased TER and disrupted VE-cadherin organization at junctions. Acetaldehyde significantly decreased TER, but inhibition of alcohol dehydrogenase or application of a superoxide dismutase mimetic failed to prevent alcohol-induced decreases in TER. Inhibition of p38 MAPK, but not MLCK or ROCK, significantly attenuated the alcohol-induced barrier dysfunction. Alcohol rapidly decreased GTP-bound Rac1 but not RhoA during the drop in TER. Activation of Epac increased TER, but did not prevent alcohol from decreasing TER. However, activation of Epac after initiation of alcohol-induced barrier dysfunction quickly resolved TER to baseline levels. Our results suggest that

Chronic and intermittent exposure to alcohol vapors: a new model of alcohol-induced osteopenia in the rat.

PubMed

Maurel, Delphine B; Jaffré, Christelle; O'Brien, Emmanuelle Simon; Tournier, Carine C; Houchi, Hakim; Benhamou, Claude-Laurent; Naassila, Mickael

2013-01-01

Different models are used to study the effects of chronic alcohol consumption on bone tissue in the rat. However, the current models take several months to show indices of osteopenia as observed in chronic drinkers. Numerous studies have supported that chronic and intermittent exposure to ethanol vapors has predictive validity as a model of alcohol dependence in humans. However, this model has never been applied to bone research to study its effects on the parameters that define osteopenia. This was the goal of this study in the rat. Male Wistar rats were exposed to ethanol vapor inhalation (n = 6) or air (controls, n = 6). Animals were exposed to chronic (11 weeks) and intermittent (14 hours a day) ethanol vapor reaching stable blood alcohol levels (BALs; 150 to 250 mg/dl) at the end of the third week of inhalation. After the sacrifice, right and left femur and tibia were dissected free of fat and connective tissue and bone mineral density (BMD) was assessed by dual X-ray absorptiometry. The microarchitecture of the femur was studied using microcomputed tomography. The BMD of the left and right femurs and the left tibia was lower in the ethanol group compared with the control group. The bone volume fraction (BV/TV) and the bone surface density (BS/TV) were lower in the ethanol group compared with control animals. The trabecular number (Tb.N) was lower in the ethanol group while the trabecular spacing was higher. The decrease in the BMD, BV/TV, and Tb.N is in the same range as what is observed in human drinkers and what is reported with other animal alcohol models (Lieber-DeCarli liquid diet, ethanol in the tap water). Therefore, this model could be useful to study the effects of chronic alcohol consumption in the bone research field and has the advantage of controlling easily targeted BALs. Copyright © 2012 by the Research Society on Alcoholism.

Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base excision repair in adult brain.

PubMed

Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J; Bergeson, Susan E; Henderson, George I; Kruman, Inna I

2012-12-21

The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr(+/-) mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain.

A Systematic Review of the Impact of Exposure to Internet-Based Alcohol-Related Content on Young People's Alcohol Use Behaviours.

PubMed

Gupta, Himanshu; Pettigrew, Simone; Lam, Tina; Tait, Robert J

2016-11-01

To conduct a systematic review of studies exploring the relationship between exposure to Internet-based alcohol-related content and alcohol use among young people. Searches of electronic databases and reference lists of relevant articles were conducted to retrieve studies of relevance up until December 2015. Full texts of the studies that met the inclusion criteria were read, appraised for quality using the Kmet forms and guidelines, and included in this review. Fifteen relevant studies were identified. The included studies were a mix of cross-sectional, longitudinal, experimental and qualitative studies conducted in the USA, the UK, Australia and New Zealand. The age range of the participants involved in these studies was 12-25 years. Included studies employed a variety of study designs and a range of different exposure variables and outcome measures. Studies demonstrated significant associations between exposure to Internet-based alcohol-related content and intentions to drink and positive attitudes towards alcohol drinking among young people. Exposure to alcohol-related content on the Internet might predispose young people to patterns of alcohol use by promoting alcohol as a natural and vital part of life. However, the research exploring the influence of this novel form of advertising on young people's alcohol use is emergent, and comprised primarily of cross-sectional studies. To evaluate the direction of the association between exposure to online alcohol-related content and alcohol use, we call for further research based on longitudinal designs. From 15 relevant studies identified, this review reports significant associations between exposure to Internet-based alcohol-related content and intentions to drink and positive attitudes towards alcohol drinking among young people, with different influences found at different stages of alcohol use. ©The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

2017-02-01

Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. Up to 40% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects (CHDs) including life-threatening outflow and valvuloseptal anomalies. Previously we established a PAE model in the avian embryo and used optical coherence tomography (OCT) imaging to assay looping-stage (early) cardiac function/structure and septation-stage (late) cardiac defects. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septae, and aortic vessels. However, supplementation with the methyl donor betaine reduced gross defects, prevented cardiac defects such as ventricular septal defects and abnormal AV valves, and normalized cardiac parameters. Immunofluorescent staining for 5-methylcytosine in transverse embryo sections also revealed that DNA methylation levels were reduced by ethanol but normalized by co-administration of betaine. Furthermore, supplementation with folate, another methyl donor, in the PAE model appeared to normalize retrograde flow levels which are typically elevated by ethanol exposure. Studies are underway to correlate retrograde flow numbers for folate with associated cushion volumes. Finally, preliminary findings have revealed that glutathione, a key endogenous antioxidant which also regulates methyl group donation, is particularly effective in improving alcohol-impacted survival and gross defect rates. Current investigations will determine whether glutathione has any positive effect on PAE-related CHDs. Our studies could have significant implications for public health, especially related to prenatal nutrition recommendations.

Drunk Bugs: Chronic Vapour Alcohol Exposure Induces Marked Changes in the Gut Microbiome in Mice

PubMed Central

Peterson, Veronica L.; Jury, Nicholas J.; Cabrera-Rubio, Raúl; Draper, Lorraine A.; Crispie, Fiona; Cotter, Paul D.; Dinan, Timothy G.; Holmes, Andrew; Cryan, John F.

2017-01-01

The gut microbiota includes a community of bacteria that and play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (Shannon and Simpson index, p<0.05) and beta (ANOSIM, p<0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p<0.001) and significant reductions in genra Clostridium IV and XIVb (Kruskal-Wallis, p<0.001), Dorea (Kruskal-Wallis, p<0.01), and Coprococcus (Kruskal-Wallis, p<0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress. PMID:28161446

Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice.

PubMed

Peterson, Veronica L; Jury, Nicholas J; Cabrera-Rubio, Raúl; Draper, Lorraine A; Crispie, Fiona; Cotter, Paul D; Dinan, Timothy G; Holmes, Andrew; Cryan, John F

2017-04-14

The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (p<0.05) and beta (p<0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p<0.001) and significant reductions in genra Clostridium IV and XIVb (p<0.001), Dorea (p<0.01), and Coprococcus (p<0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Neurobehavioral consequences of prenatal alcohol exposure: an international perspective.

PubMed

Riley, Edward P; Mattson, Sarah N; Li, Ting-Kai; Jacobson, Sandra W; Coles, Claire D; Kodituwakku, P W; Adnams, Colleen M; Korkman, Marit I

2003-02-01

This article represents the proceedings of a symposium at the 2002 Research Society on Alcoholism/International Society for Biomedical Research on Alcoholism meeting in San Francisco, CA. The organizers were Edward P. Riley and Sarah N. Mattson, and the chairperson was Edward P. Riley. The presentations were (1) Neurobehavioral deficits in alcohol-exposed South African infants: preliminary findings, by Sandra W. Jacobson, Christopher D. Molteno, Denis Viljoen, and Joseph L. Jacobson; (2) A pilot study of classroom intervention for learners with fetal alcohol syndrome in South Africa, by Colleen Adnams, M. W. Rossouw, M. D. Perold, P. W. Kodituwakku, and W. Kalberg; (3) Differential effects of prenatal alcohol exposure on fluid versus crystallized intelligence, by P. W. Kodituwakku, W. Kalberg, L. Robinson, and P. A. May; (4) Neurobehavioral outcomes of prenatal alcohol exposure: early identification of alcohol effects, by Claire D. Coles; (5) Fetal alcohol syndrome in Moscow, Russia: neuropsychology test performance, by Sarah N. Mattson, E. P. Riley, A. Matveeva, and G. Marintcheva; and (6) Long-term follow-up of Finnish children exposed to alcohol in utero in various durations, by Marit I. Korkman and I. Autti-Rämö. The discussant was Ting-Kai Li.

Longitudinal Study of Exposure to Entertainment Media and Alcohol Use Among German Adolescents

PubMed Central

Hanewinkel, Reiner; Sargent, James D.

2009-01-01

BACKGROUND Entertainment media exposure may predict teenager alcohol use, but few longitudinal studies have been reported. METHODS A longitudinal study was conducted of 2708 German adolescents aged 10 to 16 years who had never drunk alcohol. Each adolescent was surveyed at school about daily television use, whether they had a television in their bedroom, and their exposure to movie alcohol depictions. Adolescents were resurveyed 12 to 13 months later (retention rate: 85%) to determine onset of drinking alcohol without parental knowledge and binge drinking (≥5 consecutive drinks). RESULTS Overall, 885 (33%) students initiated alcohol use without parental knowledge (17% in quartile 1 movie alcohol exposure), and 387 (14%) initiated binge drinking during follow-up. After controlling for baseline covariates, exposure to movie alcohol use significantly increased percent initiating alcohol use (to 24% in exposure quartile 2, 33% in quartile 3 and 34% in quartile 4) and percent initiating binge drinking (to 8.6% in exposure quartile 2, 12% in quartile 3 and 13% in quartile 4). Having a television in the bedroom also predicted both outcomes, but daily television use did not. CONCLUSIONS Movie exposure and having a television in the bedroom are both independent predictors of onset of problematic alcohol use among German teenagers. Media restrictions could play a role in prevention. PMID:19255030

Impact of fetal alcohol exposure on body systems: A systematic review.

PubMed

Caputo, Courtney; Wood, Erin; Jabbour, Leila

2016-06-01

Review of published manuscripts on fetal alcohol exposure on several body systems. Articles in this review were found online using databases such as Medline, Medline Complete, PubMed, and Health Source: Nursing/Academic Edition. The following terms were searched: fetal alcohol spectrum disorders, fetal alcohol syndrome, prenatal alcohol exposure, and alcohol related birth defects. Thirteen articles were gathered, five original investigations and eight reviews. This review identified several abnormalities in the body systems discussed and their associations to fetal alcohol syndrome. Evidence shows that the brain was the most severely impacted organ of the body systems discussed. However, prenatal alcohol exposure causes several abnormalities within the heart, kidney, liver, gastrointestinal tract, and the endocrine systems. In addition, preventative measures need to be taken by mothers during pregnancy. Birth Defects Research (Part C), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part C) 108:174-180, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition.

PubMed

Burnett, Elizabeth J; Chandler, L Judson; Trantham-Davidson, Heather

2016-02-04

Alcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence. To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure. In particular, up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, this observation as well as other glutamatergic neuroadaptations are often circuit and cell-type specific. Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests that they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction. While pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover novel, possibly circuit

Comparison of motor delays in young children with fetal alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure.

PubMed

Kalberg, Wendy O; Provost, Beth; Tollison, Sean J; Tabachnick, Barbara G; Robinson, Luther K; Eugene Hoyme, H; Trujillo, Phyllis M; Buckley, David; Aragon, Alfredo S; May, Philip A

2006-12-01

Researchers are increasingly considering the importance of motor functioning of children with fetal alcohol spectrum disorder (FASD). The purpose of this study was to assess the motor development of young children with fetal alcohol syndrome (FAS) to determine the presence and degree of delay in their motor skills and to compare their motor development with that of matched children without FAS. The motor development of 14 children ages 20 to 68 months identified with FAS was assessed using the Vineland Adaptive Behavior Scales (VABS). In addition, 2 comparison groups were utilized. Eleven of the children with FAS were matched for chronological age, gender, ethnicity, and communication age to: (1) 11 children with prenatal alcohol exposure who did not have FAS and (2) 11 matched children without any reported prenatal alcohol exposure. The motor scores on the VABS were compared among the 3 groups. Most of the young children with FAS in this study showed clinically important delays in their motor development as measured on the VABS Motor Domain, and their fine motor skills were significantly more delayed than their gross motor skills. In the group comparisons, the young children with FAS had significantly lower Motor Domain standard (MotorSS) scores than the children not exposed to alcohol prenatally. They also had significantly lower Fine Motor Developmental Quotients than the children in both the other groups. No significant group differences were found in gross motor scores. For MotorSS scores and Fine Motor Developmental Quotients, the means and standard errors indicated a continuum in the scores from FAS to prenatal alcohol exposure to nonexposure. These findings strongly suggest that all young children with FAS should receive complete developmental evaluations that include assessment of their motor functioning, to identify problem areas and provide access to developmental intervention programs that target deficit areas such as fine motor skills. Fine motor

Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

PubMed

Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

2016-10-05

A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional inactivation of the orbitofrontal cortex disrupts context-induced reinstatement of alcohol seeking in rats.

PubMed

Bianchi, Paula Cristina; Carneiro de Oliveira, Paulo Eduardo; Palombo, Paola; Leão, Rodrigo Molini; Cogo-Moreira, Hugo; Planeta, Cleopatra da Silva; Cruz, Fábio Cardoso

2018-05-01

The high rate of relapse to drug use remains a central challenge to treating drug addiction. In human and rat models of addiction, environmental stimuli in contexts associated with previous drug use can provoke a relapse of drug seeking. Pre-clinical studies have used the ABA renewal procedure to study context-induced reinstatement of drug seeking. In the current study, we studied the role of the orbitofrontal cortex (OFC) in context-induced reinstatement to alcohol. We trained male and female rats to self-administer alcohol in context A, extinguished drug-reinforced responding in a distinct context B, and assessed context-induced reinstatement in context A or B (control group). Next, we determined the effect of context-induced renewal of alcohol-seeking behavior on the expression of Fos (a neuronal activity marker) in the OFC. Finally, we determined the effect of reversible inactivation by GABAa and GABAb receptor agonists (i.e., muscimol and baclofen, respectively) in the OFC. There were no differences between male and female rats in context-induced reinstatement of alcohol-seeking behavior. Re-exposure to Context A, but not Context B, reinstated alcohol-seeking behavior and increased expression of the neural activity marker Fos in the OFC. Reversible inactivation of the OFC with muscimol and baclofen attenuated context-induced reinstatement. Our data indicated that the OFC mediates context-induced reinstatement of alcohol-seeking behavior. Copyright © 2018 Elsevier B.V. All rights reserved.

Embryonic Alcohol Exposure Impairs the Dopaminergic System and Social Behavioral Responses in Adult Zebrafish

PubMed Central

Fernandes, Yohaan; Rampersad, Mindy

2015-01-01

Background: The zebrafish is a powerful neurobehavioral genetics tool with which complex human brain disorders including alcohol abuse and fetal alcohol spectrum disorders may be modeled and investigated. Zebrafish innately form social groups called shoals. Previously, it has been demonstrated that a single bath exposure (24 hours postfertilization) to low doses of alcohol (0, 0.25, 0.50, 0.75, and 1% vol/vol) for a short duration (2 hours) leads to impaired group forming, or shoaling, in adult zebrafish. Methods: In the current study, we immersed zebrafish eggs in a low concentration of alcohol (0.5% or 1% vol/vol) for 2 hours at 24 hours postfertilization and let the fish grow and reach adulthood. In addition to quantifying the behavioral response of the adult fish to an animated shoal, we also measured the amount of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid from whole brain extracts of these fish using high-pressure liquid chromatograph. Results: Here we confirm that embryonic alcohol exposure makes adult zebrafish increase their distance from the shoal stimulus in a dose-dependent manner. We also show that the shoal stimulus increases the amount of dopamine and 3,4-dihydroxyphenylacetic acid in the brain of control zebrafish but not in fish previously exposed to alcohol during their embryonic development. Conclusions: We speculate that one of the mechanisms that may explain the embryonic alcohol-induced impaired shoaling response in zebrafish is dysfunction of reward mechanisms subserved by the dopaminergic system. PMID:25568285

Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells

PubMed Central

Kim, Yi Young; Roubal, Ivan; Lee, Youn Soo; Kim, Jin Seok; Hoang, Michael; Mathiyakom, Nathan; Kim, Yong

2016-01-01

Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol’s effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event

Context-induced relapse to alcohol seeking after punishment in a rat model.

PubMed

Marchant, Nathan J; Khuc, Thi N; Pickens, Charles L; Bonci, Antonello; Shaham, Yavin

2013-02-01

Rat studies have demonstrated that exposure to environments associated with alcohol intake reinstates alcohol seeking after extinction of alcohol-reinforced responding in a different context. However, extinction is limited as an abstinence model, because humans typically abstain because of negative consequences associated with excessive drinking. It is currently unknown whether alcohol-associated contexts can provoke relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences in a different context. Alcohol-preferring P rats were first given home-cage access to 20% ethanol. Next, they were trained to self-administer 20% ethanol in one context (context A). Subsequently, all rats continued to self-administer alcohol in a different context (context B). For one group, 50% of alcohol-reinforced responses were punished by mild footshock; two other groups either received noncontingent shocks or no shock. A fourth group was given extinction training in context B. All rats were then tested for relapse to alcohol seeking under extinction conditions in contexts A and B. In Context B, alcohol-taking behavior was suppressed by contingent shock (punishment) and extinction training but not by noncontingent shock. In Context A, relapse to alcohol seeking was reliably observed in the punished and extinction groups; a context switch had no effect on alcohol seeking in the no-shock or noncontingent shock groups. Our data indicate that punishment-induced suppression of alcohol-taking behavior is context-dependent. We propose that our procedure can be used to explore mechanisms of context-induced relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Type of alcohol drink and exposure to violence: an emergency department study.

PubMed

Chavira, Cynthia; Bazargan-Hejazi, Shahrzad; Lin, Johnny; del Pino, Homero E; Bazargan, Mohsen

2011-08-01

We compared the prevalence of exposure to violence across different types of alcohol consumed and the association between the type of alcohol consumed and exposure to violence. A cross-sectional analysis of data collected from a sample of 295 Emergency Department (ED) patients identified as having an alcohol problem. Outcome measure include exposure to violence, and the main study predictor was "type of alcoholic drink" including: malt liquor beer (MLB), regular beer, wine cooler, wine, fortified wine or hard liquor. Using logistic regression analysis, ED patients who drank MLB in combination with other types of alcohol increased their odds of being both threatened and physically attacked by 8.5 compared to ED patients who drank other types of alcohol. Being female increased the odds of being both threatened and physically attacked by 2.5 and using illicit drugs increased the odds by 3.8. Analysis of covariance and estimated marginal means revealed that ED patients who only drank MLB had a higher exposure to violence compared to non-MLB drinkers, and that female illicit drug users who drank MLB in combination with other types of alcohol had the highest exposure to violence. MLB was identified as a predictor of the amount of exposure to violence and in particular, that the use of malt liquor beer in combination with other types of alcohol increased the risk of being both threatened and physically attacked. Implications for ED and community interventions are suggested.

Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes.

PubMed

Sinha, Rajita; Fox, Helen C; Hong, Kwang-Ik Adam; Hansen, Julie; Tuit, Keri; Kreek, Mary Jeanne

2011-09-01

Alcoholism is a chronic, relapsing illness in which stress and alcohol cues contribute significantly to relapse risk. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increased anxiety, and high alcohol craving have been documented during early alcohol recovery, but their influence on relapse risk has not been well studied. To investigate these responses in treatment-engaged, 1-month-abstinent, recovering alcohol-dependent patients relative to matched controls (study 1) and to assess whether HPA axis function, anxiety, and craving responses are predictive of subsequent alcohol relapse and treatment outcome (study 2). Experimental exposure to stress, alcohol cues, and neutral, relaxing context to provoke alcohol craving, anxiety, and HPA axis responses (corticotropin and cortisol levels and cortisol to corticotropin ratio) and a prospective 90-day follow-up outcome design to assess alcohol relapse and aftercare treatment outcomes. Inpatient treatment in a community mental health center and hospital-based research unit. Treatment-engaged alcohol-dependent individuals and healthy controls. Time to alcohol relapse and to heavy drinking relapse. Significant HPA axis dysregulation, marked by higher basal corticotropin level and lack of stress- and cue-induced corticotropin and cortisol responses, higher anxiety, and greater stress- and cue-induced alcohol craving, was seen in the alcohol-dependent patients vs the control group. Stress- and cue-induced anxiety and stress-induced alcohol craving were associated with fewer days in aftercare alcohol treatment. High provoked alcohol craving to both stress and to cues and greater neutral, relaxed-state cortisol to corticotropin ratio (adrenal sensitivity) were each predictive of shorter time to alcohol relapse. These results identify a significant effect of high adrenal sensitivity, anxiety, and increased stress- and cue-induced alcohol craving on subsequent alcohol relapse and treatment outcomes. Findings

Time trends and demographic differences in youth exposure to alcohol advertising on television.

PubMed

Ringel, Jeanne S; Collins, Rebecca L; Ellickson, Phyllis L

2006-10-01

To examine trends in youth exposure to alcohol advertising on television across different demographic groups. We used television ratings data on alcohol advertisements to examine trends in exposure between September 1998 and February 2002. Further, we explored the differences in exposure across demographic groups by examining group-level alcohol ad exposure across specific networks, program types, and times of day. We found that boys were more exposed than girls and African-Americans are more exposed than whites. Moreover, the race differential appeared to be increasing over time, whereas the gender differential appeared to increase with age. Differences in viewing patterns across race and gender contributed to the observed differences in exposure to alcohol advertising on television. These results provide guidance in identifying comparative vulnerabilities in exposure to alcohol advertising on television, and can aid in the development of strategies to inoculate youth against those vulnerabilities.

Environmental Enrichment Alters Neurotrophin Levels After Fetal Alcohol Exposure in Rats

PubMed Central

Parks, Elizabeth A.; McMechan, Andrew P.; Hannigan, John H.; Berman, Robert F.

2014-01-01

Background Prenatal alcohol exposure causes abnormal brain development, leading to behavioral deficits, some of which can be ameliorated by environmental enrichment. As both environmental enrichment and prenatal alcohol exposure can individually alter neurotrophin expression, we studied the interaction of prenatal alcohol and postweaning environmental enrichment on brain neurotrophin levels in rats. Methods Pregnant rats received alcohol by gavage, 0, 4, or 6 g / kg / d (Zero, Low, or High groups), or no treatment (Naïve group), on gestational days 8 to 20. After weaning on postnatal day 21, offspring were housed for 6 weeks in Isolated, Social, or Enriched conditions. Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were then measured in frontal cortex, occipital cortex, hippocampus, and cerebellar vermis. Results Prenatal alcohol exposure increased NGF levels in frontal cortex (High-dose group) and cerebellar vermis (High- and Low-dose groups); increased BDNF in frontal cortex, occipital cortex and hippocampus (Low-dose groups), and increased NT-3 in hippocampus and cerebellar vermis (High-dose). Environmental enrichment resulted in lower NGF, BDNF, and NT-3 levels in occipital cortex and lower NGF in frontal cortex. The only significant interaction between prenatal alcohol treatment and environment was in cerebellar vermis where NT-3 levels were higher for enriched animals after prenatal alcohol exposure, but not for animals housed under Isolated or Social conditions. Conclusions Both prenatal alcohol exposure and postweaning housing conditions alter brain neurotrophin levels, but the effects appear to be largely independent. Although environmental enrichment can improve functional outcomes, these results do not provide strong support for the hypothesis that rearing in a complex environment ameliorates prenatal alcohol effects on brain neurotrophin levels in rats. PMID:18652597

Youth exposure to alcohol use and brand appearances in popular contemporary movies.

PubMed

Dal Cin, Sonya; Worth, Keilah A; Dalton, Madeline A; Sargent, James D

2008-12-01

To describe alcohol use and alcohol brand appearances in popular movies and estimate adolescents' exposure to this alcohol-related content. Nationally representative, random-digit dialed survey in the United States and content analysis of alcohol depictions in the top 100 US box office hits each year from 1998 to 2002 and 34 top movies from early 2003. A total of 6522 US adolescents aged 10-14 years. Frequency of alcohol use and brand appearances in movies by Motion Picture Association of America (MPAA) rating. Estimated exposure to minutes of movie alcohol use and brand appearances among US adolescents in this age group. Most movies (83%, including 56.6% of G/PG-rated movies) depicted alcohol use and 52% (including 19.2% of G/PG movies) contained at least one alcohol brand appearance, which consisted of branded use by an actor 30.3% of the time. These movies exposed the average US adolescent 10-14 years of age to 5.6 [95% confidence interval (CI) 5.4, 5.7] hours of movie alcohol use and 243.8 (95% CI 238, 250) alcohol brand appearances (5 billion in total), mainly from youth-rated movies. Exposure to movie alcohol content was significantly higher among African American youth than youth of other races. Alcohol use and brand appearances are portrayed frequently in popular US movies (which are distributed world-wide). Children and adolescents in the United States are exposed to hours of alcohol use depictions and numerous brand appearances in movies and most of this exposure is from movies rated for this segment of the population.

CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

PubMed Central

BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

2010-01-01

Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

Timing of Moderate Level Prenatal Alcohol Exposure Influences Gene Expression of Sensory Processing Behavior in Rhesus Monkeys

PubMed Central

Schneider, Mary L.; Moore, Colleen F.; Larson, Julie A.; Barr, Christina S.; DeJesus, Onofre T.; Roberts, Andrew D.

2009-01-01

Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D2R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D2R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections. PMID:19936317

Prenatal alcohol exposure and long-term developmental consequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spohr, H.L.; Willms, J.; Steinhausen, H.C.

Fetal alcohol syndrome (FAS) is a leading cause of congenital mental retardation but little is known about the long-term development and adolescent outcome of children with FAS. In a 10-year follow-up study of 60 patients diagnosed as having FAS in infancy and childhood, the authors investigated the long-term sequelae of intrauterine alcohol exposure. The authors found that the characteristic craniofacial malformations of FAS diminish with time, but microcephaly and, to a lesser degree, short stature and underweight (in boys) persist; in female adolescents body weight normalizes. Persistent mental retardation is the major sequela of intrauterine alcohol exposure in many cases,more » and environmental and educational factors do not have strong compensatory effects on the intellectual development of affected children.« less

Heavy drinking, impulsivity and attentional narrowing following alcohol cue exposure.

PubMed

Hicks, Joshua A; Fields, Sherecce; Davis, William E; Gable, Philip A

2015-08-01

Research shows that alcohol-related stimuli have the propensity to capture attention among individuals motivated to consume alcohol. Research has further demonstrated that impulsive individuals are especially prone to this type of attentional bias. Recently, it is suggested that alcohol cue exposure can also produce a general narrowing of attention consistent with the activation of approach motivational states. Based on previous models of addiction and recent research on the activation of approach motivational states, we predicted that impulsive individuals would demonstrate a constriction of attentional focus in response to alcohol cue exposure. Participants (n = 392) completed a task assessing attentional breadth in response to alcohol and non-alcohol cues, followed by measures of alcohol use and impulsivity. The findings revealed that impulsivity scores predicted narrowing of attentional scope following the presentation of alcohol cues for heavier drinkers but not for light drinkers. These results suggest that impulsive individuals who drink more heavily demonstrate a narrowing of attention in the presence of alcohol-related incentive cues. Implications for how these findings might account for the link between impulsivity and alcohol use and misuse are discussed.

Betaine Attenuates Alcohol-Induced Pancreatic Steatosis.

PubMed

Yang, Wenjuan; Gao, Jinhang; Tai, Yang; Chen, Meng; Huang, Luming; Wen, Shilei; Huang, Zhiyin; Liu, Rui; Li, Jing; Tang, Chengwei

2016-07-01

To explore the effect of betaine on alcoholic pancreatic steatosis and its mechanism. Rats were randomly assigned to control, ethanol, or ethanol + betaine groups. Changes in pancreatic morphology; serum lipid levels; and pancreatic lipid, amylase and lipase levels were determined. The serum and adipose tissue adiponectin level was measured by an enzyme-linked immunoassay. Adiponectin receptor-1 (AdipoR1), AdipoR2, sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, and fatty acid synthetase expression levels were quantified. The SREBP-1c expression in SW1990 cells treated with various concentrations of ethanol or ethanol plus betaine and/or adiponectin was assessed. Alcohol-induced changes in pancreatic morphology were attenuated by betaine. Pancreatic triglyceride, free fatty acid and expression levels of SREBP-1c and fatty acid synthetase were elevated after ethanol feeding but remained at control levels after betaine supplementation. Alcohol-induced decreases in serum and adipose tissue adiponectin, pancreatic AdipoR1, amylase, and lipase were attenuated by betaine. Serum triglyceride and free fatty acid levels were elevated after alcohol consumption and remained higher after betaine supplementation compared with controls. Betaine and/or adiponectin suppressed alcohol-induced SREBP-1c upregulation in vitro. Betaine attenuated alcoholic-induced pancreatic steatosis most likely by suppressing pancreatic SREBP-1c both directly and through the restoration of adiponectin signaling.

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

PubMed Central

Sari, Youssef; Chiba, Tomohiro; Yamada, Marina; Rebec, George V.; Aiso, Sadakazu

2009-01-01

Fetal alcohol exposure is known to induce cell death through apoptosis. We found that colivelin (CLN), a novel peptide with the sequence SALLRSIPAPAGASRLLLLTGEIDLP, prevents this apoptosis. Our initial experiment revealed that CLN enhanced the viability of primary cortical neurons exposed to alcohol. We then used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying these neuroprotective effects. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) 25% (4.49%, v/v) ethanol derived calories; (2) pair-fed control; (3) normal chow; (4) ALC combined with administration (i.p.) of CLN (20 μg/20 g body weight); and (5) pair-fed combined with administration (i.p.) of CLN (20 μg/20 g body weight). On E13, fetal brains were collected and assayed for TUNEL staining, caspase-3 colorimetric assay, ELISA, and MSD electrochemiluminescence. CLN blocked the alcohol-induced decline in brain weight and prevented alcohol-induced: apoptosis, activation of caspase-3 and increases of cytosolic cytochrome c, and decreases of mitochondrial cytochrome c. Analysis of proteins in the upstream signaling pathway revealed that CLN down-regulated the phosphorylation of the c-Jun N-terminal kinase. Moreover, CLN prevented alcohol-induced reduction in phosphorylation of BAD protein. Thus, CLN appears to act directly on upstream signaling proteins to prevent alcohol-induced apoptosis. Further assessment of these proteins and their signaling mechanisms is likely to enhance development of neuroprotective therapies. PMID:19782727

Neonatal Alcohol Exposure Permanently Disrupts the Circadian Properties and Photic Entrainment of the Activity Rhythm in Adult Rats

PubMed Central

Allen, Gregg C.; West, James R.; Chen, Wei-Jung A.; Earnest, David J.

2009-01-01

Background Alcohol exposure during the period of rapid brain development produces structural damage in different brain regions, including the suprachiasmatic nucleus (SCN), that may have permanent neurobehavioral consequences. Thus, this study examined the long-term effects of neonatal alcohol exposure on circadian behavioral activity in adult rats. Methods Artificially reared Sprague-Dawley rat pups were exposed to alcohol (EtOH; 4.5 g/kg/day) or isocaloric milk formula (gastrostomy control; GC) on postnatal days 4–9. At 2 months of age, rats from the EtOH, GC, and suckle control (SC) groups were housed individually, and properties of the circadian rhythm in wheel-running behavior were continuously analyzed during exposure to a 12-hr light:12-hr dark photoperiod (LD 12:12) or constant darkness (DD). Results Neonatal alcohol exposure had distinctive effects on the rhythmic properties and quantitative parameters of adult wheel-running behavior. EtOH-treated animals were distinguished by unstable and altered entrainment to LD 12:12 such that their daily onsets of activity were highly variable and occurred at earlier times relative to control animals. In DD, circadian regulation of wheel-running behavior was altered by neonatal alcohol exposure such that the free-running period of the activity rhythm was shorter in EtOH-exposed rats than in control animals. Total amount of daily wheel-running activity in EtOH-treated rats was greater than that observed in the SC group. In addition, the circadian activity patterns of EtOH-exposed rats were fragmented such that the duration of the active phase and the number of activity bouts per day were increased. Conclusions These data indicate that neonatal alcohol exposure produces permanent changes in the circadian regulation of the rat activity rhythm and its entrainment to LD cycles. These long-term alterations in circadian behavior, along with the developmental alcohol-induced changes in SCN endogenous rhythmicity, may have

Apoptosis of enterocytes and nitration of junctional complex proteins promote alcohol-induced gut leakiness and liver injury.

PubMed

Cho, Young-Eun; Yu, Li-Rong; Abdelmegeed, Mohamed A; Yoo, Seong-Ho; Song, Byoung-Joon

2018-07-01

Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherens junction (AJ) proteins in binge alcohol-induced gut leakiness. The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses. Binge alcohol exposure caused apoptosis of gut enterocytes with elevated serum endotoxin and liver injury. The levels of intestinal CYP2E1, iNOS, nitrated proteins and apoptosis-related marker proteins were significantly elevated in binge alcohol-exposed rodents. Differential, quantitative mass-spectral analyses of the TJ-enriched fractions of intestinal epithelial layers revealed that several TJ, AJ and desmosome proteins were decreased in binge alcohol-exposed rats compared to controls. Consistently, the levels of TJ proteins (claudin-1, claudin-4, occludin and zonula occludens-1), AJ proteins (β-catenin and E-cadherin) and desmosome plakoglobin were very low in binge alcohol-exposed rats, wild-type mice, and autopsied human ileums but not in Cyp2e1-null mice. Additionally, pretreatment with specific inhibitors of CYP2E1 and iNOS prevented disorganization and/or degradation of TJ proteins in alcohol-exposed T84 colonic cells. Furthermore, immunoprecipitation followed by immunoblot confirmed that intestinal TJ and AJ proteins were nitrated and degraded via ubiquitin-dependent proteolysis, resulting in their decreased levels. These results demonstrated for the first time the critical roles of CYP2E1, apoptosis of enterocytes, and nitration followed by ubiquitin-dependent proteolytic degradation of the

Youth Exposure to Alcohol Use and Brand Appearances in Popular Contemporary Movies

PubMed Central

DAL CIN, Sonya; WORTH, Keilah A.; DALTON, Madeline A.; SARGENT, James D.

2010-01-01

Aims To describe alcohol use and alcohol brand appearances in popular movies and estimate adolescents’ exposure to this alcohol-related content. Design and setting Nationally representative, random-digit dialed survey in the United States and content analysis of alcohol depictions in the top 100 U.S. box office hits each year from 1998 to 2002 and 34 top movies from early 2003. Participants 6522 U.S. adolescents aged 10-14. Measurements Frequency of alcohol use and brand appearances in movies by Motion Picture Association of America (MPAA) rating. Estimated exposure to minutes of movie alcohol use and brand appearances among U.S. adolescents in this age group. Findings Most movies (83%, including 57% of G/PG-rated movies) depicted alcohol use and 52% (including 19% of G/PG movies) contained at least one alcohol brand appearance, which consisted of branded use by an actor 30% of the time. These movies exposed the average U.S. adolescent 10-14 years of age to 5.6 (95% CI 5.4,5.7) hours of movie alcohol use and 244 (95% CI 238,250) alcohol brand appearances (5 billion in total), mostly from youth-rated movies. Exposure to movie alcohol content was significantly higher among African American youth than youth of other races. Conclusions Alcohol use and brand appearances are frequently portrayed in popular U.S. movies (which are distributed worldwide). Children and adolescents in the U.S. are exposed to hours of alcohol use depictions and numerous brand appearances in movies and most of this exposure is from movies rated for this segment of the population. PMID:18705684

Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms

PubMed Central

Gangisetty, Omkaram; Wynne, Olivia; Jabbar, Shaima; Nasello, Cara; Sarkar, Dipak K.

2015-01-01

Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells. PMID:26509893

Alcohol, Methamphetamine, and Marijuana Exposure Have Distinct Effects on the Human Placenta.

PubMed

Carter, R Colin; Wainwright, Helen; Molteno, Christopher D; Georgieff, Michael K; Dodge, Neil C; Warton, Fleur; Meintjes, Ernesta M; Jacobson, Joseph L; Jacobson, Sandra W

2016-04-01

Animal studies have demonstrated adverse effects of prenatal alcohol exposure on placental development, but few studies have examined these effects in humans. Little is known about effects of prenatal exposure to methamphetamine, marijuana, and cigarette smoking on placental development. Placentas were collected from 103 Cape Coloured (mixed ancestry) pregnant women recruited at their first antenatal clinic visit in Cape Town, South Africa. Sixty-six heavy drinkers and 37 nondrinkers were interviewed about their alcohol, cigarette smoking, and drug use at 3 antenatal visits. A senior pathologist, blinded to exposure status, performed comprehensive pathology examinations on each placenta using a standardized protocol. In multivariable regression models, effects of prenatal exposure were examined on placental size, structure, and presence of infections and meconium. Drinkers reported a binge pattern of heavy drinking, averaging 8.0 drinks/occasion across pregnancy on 1.4 d/wk. 79.6% smoked cigarettes; 22.3% used marijuana; and 17.5% used methamphetamine. Alcohol exposure was related to decreased placental weight and a smaller placenta-to-birthweight ratio. By contrast, methamphetamine was associated with larger placental weight and a larger placenta-to-birthweight ratio. Marijuana was also associated with larger placental weight. Alcohol exposure was associated with increased risk of placental hemorrhage. Prenatal alcohol, drug, and cigarette use were not associated with chorioamnionitis, villitis, deciduitis, or maternal vascular underperfusion. Alcohol and cigarette smoking were associated with a decreased risk of intrauterine passing of meconium, a sign of acute fetal stress and/or hypoxia; methamphetamine, with an increased risk. This is the first human study to show that alcohol, methamphetamine, and marijuana were associated with distinct patterns of pathology, suggesting different mechanisms mediating their effects on placental development. Given the growing

Associations of alcohol use with mental health and alcohol exposure among school-going students in Cambodia.

PubMed

Peltzer, Karl; Pengpid, Supa; Tepirou, Chher

2016-12-01

The aim of this study was to examine the associations of alcohol use with sociodemographic factors, mental health and alcohol exposure among school-going adolescents in Cambodia. The analysis included 3,806 school children, mean age 15.7 years (SD=1.8), from Cambodia who participated in the "Global School-based Student Health Survey" (GSHS) in 2013. The results indicate that overall, 10.0% of the students reported current alcohol use, 10.8% lifetime drunkenness, and 2.8% problem drinking. In multivariate logistic regression analysis, sociodemographic factors (older age and being male), mental health and other variables (bullying victimization, OR (odds ratio) = 1.99; 95% Confidence Interval (CI) [1.50, 2.65] and OR = 2.15; 95% CI [1.58, 3.21], respectively; having attempted suicide, OR = 2.04; 95% CI [1.35, 3.08] and OR = 2.06; 95% CI [1.29, 3.28], respectively and illicit drug use, OR = 4.97; 95% CI [2.41, 10.24] OR = 5.05; 95% CI [2.14, 11.98], respectively) and alcohol exposure variables (peer influence on drinking alcohol, OR = 6.68; 95% CI [4.75, 9.39] and OR = 7.83; 95% CI [5.73, 10.66], respectively and daily or almost daily to alcohol advertising in the past 30 days OR = 1.61; 95% CI [1.03, 2.51] and OR = 2.30; 95% CI [1.40, 3.77], respectively) were significantly positively associated with current alcohol use and drunkenness. Moreover, older age, being male, bullying victimization, having close friends, suicide attempt, drug use, father or male guardian drinks alcohol and peer influence were associated with problem drinking. There is a need to implement public health interventions with a special focus on the determinants of alcohol consumption, including exposure to alcohol advertising, in this age group.

Neurobiology and neurodevelopmental impact of childhood traumatic stress and prenatal alcohol exposure.

PubMed

Henry, Jim; Sloane, Mark; Black-Pond, Connie

2007-04-01

Research reveals that prenatal alcohol exposure and child trauma (i.e., abuse, neglect, sexual abuse) can have deleterious effects on child development across multiple domains. This study analyzed the impact on childhood neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience compared to postnatal traumatic experience alone. Although the harmful effects of both have been well documented individually, there is no research documenting the concurrent effects of prenatal alcohol exposure and postnatal trauma on a child's developmental process. Transdisciplinary assessment of the children included the core disciplines of medicine, speech-language pathology, occupational therapy, social work, and psychology. Medical examination, standardized developmental and intelligence testing, projective tools, parent questionnaires, and psychosocial interviews provided information in the primary developmental areas. Findings indicated that children who had been exposed prenatally to alcohol along with postnatal traumatic experience had lower intelligence scores and more severe neurodevelopmental deficits in language, memory, visual processing, motor skills, and attention than did traumatized children without prenatal alcohol exposure, as well as greater oppositional/defiant behavior, inattention, hyperactivity, impulsivity, and social problems. Successful teacher and speech-language pathologist interventions with traumatized children with prenatal alcohol exposure demand a paradigm shift that requires the development of new perspectives and ongoing training.

Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

PubMed Central

Gan, Gabriela; Sterzer, Philipp; Marxen, Michael; Zimmermann, Ulrich S; Smolka, Michael N

2015-01-01

Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs non-provoking condition with a variant of the Taylor aggression paradigm (TAP) allowing to differentiate between reactive (provoked) and proactive (unprovoked) aggression. In a placebo-controlled cross-over design with moderate alcohol intoxication (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking conditions and alcohol vs placebo increased aggression and decreased brain responses in the anterior cingulate cortex/dorso-medial PFC (provokingalcoholalcohol specifically increased proactive (unprovoked) but not reactive (provoked) aggression (alcohol × provocation interaction). However, investigation of inter-individual differences revealed (1) that pronounced alcohol-induced proactive aggression was linked to higher levels of aggression under placebo, and (2) that pronounced alcohol-induced reactive aggression was related to increased amygdala and ventral striatum reactivity under alcohol, providing evidence for their role in human alcohol-induced reactive aggression. Our findings suggest that in healthy young adults a liability for alcohol-induced aggression in a non-provoking context might depend on overall high levels of aggression, but on alcohol-induced increased striatal and amygdala reactivity when triggered by provocation. PMID:25971590

Industry self-regulation of alcohol marketing: a systematic review of content and exposure research.

PubMed

Noel, Jonathan K; Babor, Thomas F; Robaina, Katherine

2017-01-01

With governments relying increasingly upon the alcohol industry's self-regulated marketing codes to restrict alcohol marketing activity, there is a need to summarize the findings of research relevant to alcohol marketing controls. This paper provides a systematic review of studies investigating the content of, and exposure to, alcohol marketing in relation to self-regulated guidelines. Peer-reviewed papers were identified through four literature search engines: SCOPUS, Web of Science, PubMed and PsychINFO. Non-peer-reviewed reports produced by public health agencies, alcohol research centers, non-governmental organizations and government research centers were also identified. Ninety-six publications met the inclusion criteria. Of the 19 studies evaluating a specific marketing code and 25 content analysis studies reviewed, all detected content that could be considered potentially harmful to children and adolescents, including themes that appeal strongly to young men. Of the 57 studies of alcohol advertising exposure, high levels of youth exposure and high awareness of alcohol advertising were found for television, radio, print, digital and outdoor advertisements. Youth exposure to alcohol advertising has increased over time, even as greater compliance with exposure thresholds has been documented. Violations of the content guidelines within self-regulated alcohol marketing codes are highly prevalent in certain media. Exposure to alcohol marketing, particularly among youth, is also prevalent. Taken together, the findings suggest that the current self-regulatory systems that govern alcohol marketing practices are not meeting their intended goal of protecting vulnerable populations. © 2016 Society for the Study of Addiction.

Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats.

PubMed

Thomas, Jennifer D; Garrison, Megan; O'Neill, Teresa M

2004-01-01

Children exposed to alcohol prenatally suffer from a variety of behavioral alterations, including hyperactivity and learning deficits. Given that women continue to drink alcohol during pregnancy, it is critical that effective interventions and treatments be identified. Previously, we reported that early postnatal choline supplementation can reduce the severity of learning deficits in rats exposed to alcohol prenatally. The present study examined whether choline supplementation can reduce the severity of behavioral alterations associated with alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4-9 via an artificial rearing procedure. Artificially reared and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4-30, whereas the other half received saline vehicle injections. On PD 31-34, after choline treatment was complete, activity level was monitored and, on PD 40-42, subjects were tested on a serial spatial discrimination reversal learning task. Subjects exposed to alcohol were significantly hyperactive compared to controls. The severity of ethanol-induced hyperactivity was attenuated with choline treatment. In addition, subjects exposed to ethanol during the neonatal period committed a significantly greater number of perseverative-type errors on the reversal learning task compared to controls. Exposure to choline significantly reduced the number of ethanol-related errors. Importantly, these behavioral changes were not due to the acute effects of choline, but were related to long-lasting organizational effects of early choline supplementation. These data suggest that early dietary interventions may reduce the severity of fetal alcohol effects.

Early adolescent exposure to alcohol advertising and its relationship to underage drinking.

PubMed

Collins, Rebecca L; Ellickson, Phyllis L; McCaffrey, Daniel; Hambarsoomians, Katrin

2007-06-01

To determine whether early adolescents who are exposed to alcohol marketing are subsequently more likely to drink. Recent studies suggest that exposure to alcohol ads has a limited influence on drinking in mid-adolescence. Early adolescents may be more vulnerable to alcohol advertising effects. Two in-school surveys of 1786 South Dakota youth measured exposure to television beer advertisements, alcohol ads in magazines, in-store beer displays and beer concessions, radio-listening time, and ownership of beer promotional items during 6th grade, and drinking intentions and behavior at 7th grade. Multivariate regression equations predicted the two drinking outcomes using the advertising exposure variables and controlling for psychosocial factors and prior drinking. After adjusting for covariates, the joint effect of exposure to advertising from all six sources at grade 6 was strongly predictive of grade 7 drinking and grade 7 intentions to drink. Youth in the 75th percentile of alcohol marketing exposure had a predicted probability of drinking that was 50% greater than that of youth in the 25th percentile. Although causal effects are uncertain, policy makers should consider limiting a variety of marketing practices that could contribute to drinking in early adolescence.

Youth Exposure to Alcohol Advertising in National Magazines in the United States, 2001-2011.

PubMed

Ross, Craig S; Henehan, Elizabeth R; Jernigan, David H

2017-01-01

To update public health surveillance of alcohol advertising to underage populations by assessing alcohol industry compliance with their voluntary guidelines for US magazine advertisements from 2001 to 2011. Using advertising industry standard sources The Nielsen Company and MediaMark, we evaluated youth exposure to alcohol advertising, and relative advertising exposure of youths versus adults, in 168 national magazines. From 2001 to 2011, magazine alcohol advertising seen by youths declined by 62.9%, from 5.4 billion impressions (single person seeing a single advertisement) to 2.0 billion impressions. Most alcohol advertising (65.1% of ads) was for spirits (e.g., vodka, whiskey). Since 2008, alcohol companies achieved 100% compliance with their limited guidelines. However, youths were overexposed to magazine advertising relative to adults on average 73% of the time. Despite improving compliance with placement guidelines in national editions of the 168 measured magazines, most youth exposure to magazine alcohol advertising exceeded adult exposure, per capita. If alcohol companies adopted stricter guidelines based on public health risk assessments, youths would not be overexposed to alcohol advertising in magazines.

Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure.

PubMed

Comasco, E; Rangmar, J; Eriksson, U J; Oreland, L

2018-01-01

Several explanations for the diverse results in research on foetal alcohol spectrum disorders or alcohol-related neurodevelopmental disorder might be at hand: timing, amount and patterns of alcohol exposure, as well as complex epigenetic responses. The genetic background of the offspring and its interaction with other prenatal and post-natal environmental cues are likely also of importance. In the present report, key findings about the possible effects of low and moderate doses of maternal alcohol intake on the neuropsychological development of the offspring are reviewed and plausible mechanisms discussed. Special focus is put on the serotonergic system within developmental and gene-environment frameworks. The review also suggests guidelines for future studies and also summarizes some of to-be-answered questions of relevance to clinical practice. Contradictory findings and paucity of studies on the effects of exposure to low alcohol levels during foetal life for the offspring's neuropsychological development call for large prospective studies, as well as for studies including neuroimaging and multi-omics analyses to dissect the neurobiological underpinnings of alcohol exposure-related phenotypes and to identify biomarkers. Finally, it remains to be investigated whether any safe threshold of alcohol drinking during pregnancy can be identified. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Pharmacologically induced alcohol craving in treatment seeking alcoholics correlates with alcoholism severity, but is insensitive to acamprosate

PubMed Central

Umhau, John C; Schwandt, Melanie L; Usala, Julie; Geyer, Christopher; Singley, Erick; George, David T; Heilig, Markus

2011-01-01

Modulation of alcohol craving induced by challenge stimuli may predict the efficacy of new pharmacotherapies for alcoholism. We evaluated two pharmacological challenges, the α2-adrenergic antagonist yohimbine, which reinstates alcohol seeking in rats, and the serotonergic compound meta-chlorophenylpiperazine (mCPP), previously reported to increase alcohol craving in alcoholics. To assess the predictive validity of this approach, the approved alcoholism medication acamprosate was evaluated for its ability to modulate challenge-induced cravings. A total of 35 treatment seeking alcohol dependent inpatients in early abstinence were randomized to placebo or acamprosate (2997 mg daily). Following two weeks of medication, subjects underwent three challenge sessions with yohimbine, mCPP or saline infusion under double blind conditions, carried out in counterbalanced order, and separated by at least 5 days. Ratings of cravings and anxiety, as well as biochemical measures were obtained. In all, 25 subjects completed all three sessions and were included in the analysis. Cravings were modestly, but significantly higher following both yohimbine and mCPP challenge compared with saline infusion. The mCPP, but not yohimbine significantly increased anxiety ratings. Both challenges produced robust ACTH, cortisol and prolactin responses. There was a significant correlation between craving and the degree of alcoholism severity. Acamprosate administration did not influence craving. Both yohimbine and mCPP challenges lead to elevated alcohol craving in a clinical population of alcoholics, and these cravings correlate with alcoholism severity. Under the experimental conditions used, alcohol cravings induced by these two stimuli are not sensitive to acamprosate at clinically used doses. PMID:21289601

Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure.

PubMed

Panczakiewicz, Amy L; Glass, Leila; Coles, Claire D; Kable, Julie A; Sowell, Elizabeth R; Wozniak, Jeffrey R; Jones, Kenneth Lyons; Riley, Edward P; Mattson, Sarah N

2016-09-01

Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented; however, the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Subjects were 407 youth with prenatal alcohol exposure (n = 192) and controls (n = 215). Two age groups (child [5 to 7 years] or adolescent [10 to 16 years]) and both sexes were included. All subjects completed standardized neuropsychological testing, and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) multivariate analyses of variance (MANOVAs). Significant effects were followed by univariate analyses. No 3-way or 2-way interactions were significant. The main effect of group was significant in all 3 MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on 3 measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual spatial scores and fewer somatic complaints than females. Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for nonexposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not

Young Adults' Exposure to Alcohol- and Marijuana-Related Content on Twitter.

PubMed

Cabrera-Nguyen, E Peter; Cavazos-Rehg, Patricia; Krauss, Melissa; Bierut, Laura J; Moreno, Megan A

2016-03-01

Twitter is among the most popular social media platforms used by young adults, yet it has been underutilized in substance use research compared with older platforms (e.g., MySpace and Facebook). We took a first step toward studying the associations between exposure to pro-alcohol- and marijuana-related content among young adults via Twitter and current heavy episodic drinking and current marijuana use, respectively. We conducted an online survey of 587 (254 men, 333 women) Twitter users between ages 18 and 25 years in February 2014 using an online survey system that has been previously used in research on health behaviors and attitudes. Current heavy episodic drinking was significantly associated with higher levels of exposure to pro-alcohol content. Similarly, current marijuana use was significantly associated with higher levels of exposure to pro-marijuana content. Our findings suggest that in-depth research regarding young adults' exposure to pro-alcohol- and marijuana-related content via Twitter may provide a foundation for developing effective prevention messages on this social media platform to counter the pro-alcohol and marijuana messages.

Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice

PubMed Central

Robins, Meridith T.; Lu, Julie

2016-01-01

The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations. PMID:27380261

Induced theta oscillations as biomarkers for alcoholism.

PubMed

Andrew, Colin; Fein, George

2010-03-01

Studies have suggested that non-phase-locked event-related oscillations (ERO) in target stimulus processing might provide biomarkers of alcoholism. This study investigates the discriminatory power of non-phase-locked oscillations in a group of long-term abstinent alcoholics (LTAAs) and non-alcoholic controls (NACs). EEGs were recorded from 48 LTAAs and 48 age and gender comparable NACs during rest with eyes open (EO) and during the performance of a three-condition visual target detection task. The data were analyzed to extract resting power, ERP amplitude and non-phase-locked ERO power measures. Data were analyzed using MANCOVA to determine the discriminatory power of induced theta ERO vs. resting theta power vs. P300 ERP measures in differentiating the LTAA and NAC groups. Both groups showed significantly more theta power in the pre-stimulus reference period of the task vs. the resting EO condition. The resting theta power did not discriminate the groups, while the LTAAs showed significantly less pre-stimulus theta power vs. the NACs. The LTAAs showed a significantly larger theta event-related synchronization (ERS) to the target stimulus vs. the NACs, even after accounting for pre-stimulus theta power levels. ERS to non-target stimuli showed smaller induced oscillations vs. target stimuli with no group differences. Alcohol use variables, a family history of alcohol problems, and the duration of alcohol abstinence were not associated with any theta power measures. While reference theta power in the task and induced theta oscillations to target stimuli both discriminate LTAAs and NACs, induced theta oscillations better discriminate the groups. Induced theta power measures are also more powerful and independent group discriminators than the P3b amplitude. Induced frontal theta oscillations promise to provide biomarkers of alcoholism that complement the well-established P300 ERP discriminators.

Conditions for Further Study: Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure

ERIC Educational Resources Information Center

Hart, Shelley R.; Harrison, Molly J.

2017-01-01

The Alcohol Abuse and Alcoholism branch of the National Institute of Health (NIH) indicates that there is no known safe level of alcohol consumption during pregnancy (NIH, 2015). Prenatal alcohol exposure (PAE) is the leading preventable cause of birth defects and neurodevelopmental abnormalities in the United States, which is not surprising given…

Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure.

PubMed

Balaraman, Sridevi; Idrus, Nirelia M; Miranda, Rajesh C; Thomas, Jennifer D

2017-05-01

Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol's long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4-9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was attenuated with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p < 0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by

Chronic alcohol exposure differentially affects activation of female locus coeruleus neurons and the subcellular distribution of corticotropin releasing factor receptors.

PubMed

Retson, T A; Reyes, B A; Van Bockstaele, E J

2015-01-02

Understanding the neurobiological bases for sex differences in alcohol dependence is needed to help guide the development of individualized therapies for alcohol abuse disorders. In the present study, alcohol-induced adaptations in (1) anxiety-like behavior, (2) patterns of c-Fos activation and (3) subcellular distribution of corticotropin releasing factor receptor in locus coeruleus (LC) neurons was investigated in male and female Sprague-Dawley rats that were chronically exposed to ethanol using a liquid diet. Results confirm and extend reports by others showing that chronic ethanol exposure produces an anxiogenic-like response in both male and female subjects. Ethanol-induced sex differences were observed with increased c-Fos expression in LC neurons of female ethanol-treated subjects compared to controls or male subjects. Results also reveal sex differences in the subcellular distribution of the CRFr in LC-noradrenergic neurons with female subjects exposed to ethanol exhibiting a higher frequency of plasmalemmal CRFrs. These adaptations have implications for LC neuronal activity and its neural targets across the sexes. Considering the important role of the LC in ethanol-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis, the present results indicate important sex differences in feed-forward regulation of the HPA axis that may render alcohol dependent females more vulnerable to subsequent stress exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

Early Adolescent Exposure to Alcohol Advertising and Its Relationship to Underage Drinking

PubMed Central

Collins, Rebecca L.; Ellickson, Phyllis L.; McCaffrey, Daniel; Hambarsoomians, Katrin

2009-01-01

Purpose To determine whether early adolescents who are exposed to alcohol marketing are subsequently more likely to drink. Recent studies suggest that exposure to alcohol ads has a limited influence on drinking in mid-adolescence. Early adolescents may be more vulnerable to alcohol advertising effects. Methods Two in-school surveys of 1,786 South Dakota youth measured exposure to television beer advertisements, alcohol ads in magazines, in-store beer displays and beer concessions, radio-listening time, and ownership of beer promotional items during sixth grade, and drinking intentions and behavior at seventh grade. Multivariate regression equations predicted the two drinking outcomes using the advertising exposure variables and controlling for psychosocial factors and prior drinking. Results After adjusting for covariates, the joint effect of exposure to advertising from all six sources at Grade 6 was strongly predictive of Grade 7 drinking and Grade 7 intentions to drink. Youth in the 75th percentile of alcohol marketing exposure had a predicted probability of drinking that was 50% greater than that of youth in the 25th percentile. Conclusions Although causal effects are uncertain, policy makers should consider limiting a variety of marketing practices that could contribute to drinking in early adolescence. PMID:17531759

Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice.

PubMed

Wieczorek, Lindsay; Fish, Eric W; O'Leary-Moore, Shonagh K; Parnell, Scott E; Sulik, Kathleen K

2015-05-01

The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Children with Heavy Prenatal Alcohol Exposure Experience Reduced Control of Isotonic Force

PubMed Central

Nguyen, Tanya T.; Levy, Susan S.; Riley, Edward P.; Thomas, Jennifer D.; Simmons, Roger W.

2013-01-01

Background Heavy prenatal alcohol exposure can result in diverse and extensive damage to the central nervous system, including the cerebellum, basal ganglia, and cerebral cortex. Given that these brain regions are involved in the generation and maintenance of motor force, we predicted that prenatal alcohol exposure would adversely affect this parameter of motor control. We previously reported that children with gestational alcohol exposure experience significant deficits in regulating isometric (i.e., constant) force. The purpose of the present study was to determine if these children exhibit similar deficits when producing isotonic (i.e., graded) force. Methods Children with heavy prenatal alcohol exposure and typically developing children completed a series of isotonic force contractions by exerting force on a load cell to match a criterion target force displayed on a computer monitor. Two levels of target force (5% or 20% of maximum voluntary force) were investigated in combination with varying levels of visual feedback. Results Compared to controls, children with heavy prenatal alcohol exposure generated isotonic force signals that were less accurate, more variable, and less complex in the time domain compared to control children. Specifically, interactions were found between group and visual feedback for response accuracy and signal complexity, suggesting that these children have greater difficulty altering their motor output when visual feedback is low. Conclusions These data suggest that prenatal alcohol exposure produces deficits in regulating isotonic force, which presumably result from alcohol-related damage to developing brain regions involved in motor control. These children will most likely experience difficulty performing basic motor skills and daily functional skills that require coordination of finely graded force. Therapeutic strategies designed to increase feedback and, consequently, facilitate visual-motor integration could improve isotonic force

Strengthening the Case: Prenatal Alcohol Exposure is Associated with Increased Risk for Conduct Disorder

PubMed Central

Disney, Elizabeth R.; Iacono, William; McGue, Matthew; Tully, Erin; Legrand, Lisa

2008-01-01

Objective The purpose of this study was to examine the relationship between alcohol exposure in pregnancy and offspring conduct disorder (CD) symptoms in adolescence, and to examine how much this increasingly well-known association may be mediated by maternal and paternal externalizing diagnoses, including lifetime maternal and paternal alcohol and drug abuse/dependence diagnoses as well as antisocial disorders. Few other studies have examined the contribution of these diagnoses across both parents. Method A population sample of 1252 adolescents (53.8% female; drawn from the Minnesota Twin Family Study) as well as both their parents completed structured diagnostic interviews to generate lifetime psychiatric diagnoses; mothers were also retrospectively interviewed about alcohol and nicotine use during pregnancy. Linear regression models were used to test the effects of prenatal alcohol exposure on adolescents' CD symptoms. Results Prenatal exposure to alcohol was associated with higher levels of CD symptoms in offspring, even after statistically controlling for the effects of parental externalizing disorders (i.e., illicit substance use disorders, alcohol dependence, and antisocial/behavioral disorders), prenatal nicotine exposure, monozygosity, gestational age, and birth weight. Conclusions Prenatal alcohol exposure contributes to increased risk for CD in offspring. PMID:19047223

Neurobiology and Neurodevelopmental Impact of Childhood Traumatic Stress and Prenatal Alcohol Exposure

ERIC Educational Resources Information Center

Henry, Jim; Sloane, Mark; Black-Pond, Connie

2007-01-01

Purpose: Research reveals that prenatal alcohol exposure and child trauma (i.e., abuse, neglect, sexual abuse) can have deleterious effects on child development across multiple domains. This study analyzed the impact on childhood neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience compared to postnatal traumatic…

Gaze-evoked nystagmus induced by alcohol intoxication.

PubMed

Romano, Fausto; Tarnutzer, Alexander A; Straumann, Dominik; Ramat, Stefano; Bertolini, Giovanni

2017-03-15

The cerebellum is the core structure controlling gaze stability. Chronic cerebellar diseases and acute alcohol intoxication affect cerebellar function, inducing, among others, gaze instability as gaze-evoked nystagmus. Gaze-evoked nystagmus is characterized by increased centripetal eye-drift. It is used as an important diagnostic sign for patients with cerebellar degeneration and to assess the 'driving while intoxicated' condition. We quantified the effect of alcohol on gaze-holding using an approach allowing, for the first time, the comparison of deficits induced by alcohol intoxication and cerebellar degeneration. Our results showed that alcohol intoxication induces a two-fold increase of centripetal eye-drift. We establish analysis techniques for using controlled alcohol intake as a model to support the study of cerebellar deficits. The observed similarity between the effect of alcohol and the clinical signs observed in cerebellar patients suggests a possible pathomechanism for gaze-holding deficits. Gaze-evoked nystagmus (GEN) is an ocular-motor finding commonly observed in cerebellar disease, characterized by increased centripetal eye-drift with centrifugal correcting saccades at eccentric gaze. With cerebellar degeneration being a rare and clinically heterogeneous disease, data from patients are limited. We hypothesized that a transient inhibition of cerebellar function by defined amounts of alcohol may provide a suitable model to study gaze-holding deficits in cerebellar disease. We recorded gaze-holding at varying horizontal eye positions in 15 healthy participants before and 30 min after alcohol intake required to reach 0.6‰ blood alcohol content (BAC). Changes in ocular-motor behaviour were quantified measuring eye-drift velocity as a continuous function of gaze eccentricity over a large range (±40 deg) of horizontal gaze angles and characterized using a two-parameter tangent model. The effect of alcohol on gaze stability was assessed analysing: (1

Early alcohol exposure impairs ocular dominance plasticity throughout the critical period.

PubMed

Medina, Alexandre E; Ramoa, Ary S

2005-06-09

Animal models of fetal alcohol syndrome (FAS) have revealed an impairment of sensory neocortex plasticity. Here, we examine whether early alcohol exposure leads to a permanent impairment of ocular dominance plasticity (OD) or to an alteration in the timing of the critical period. Ferrets were exposed to alcohol during a brief period of development prior to eye opening and effects of monocular deprivation examined during early, mid and late critical period. Single-unit electrophysiology revealed markedly reduced OD plasticity at every age examined. This finding provides evidence that early alcohol exposure does not affect the timing or duration of the critical period of OD plasticity and suggests an enduring impairment of neural plasticity in FAS.

Transcriptome changes induced in vitro by alcohol-containing mouthwashes in normal and dysplastic oral keratinocytes.

PubMed

Fox, Simon A; Currie, Sean S; Dalley, Andrew J; Farah, Camile S

2018-05-01

The role of alcohol-containing mouthwash as a risk factor for the development of oral cancer is a subject of conflicting epidemiological evidence in the literature despite alcohol being a recognised carcinogen. The aim of this study was to use in vitro models to investigate mechanistic and global gene expression effects of exposure to alcohol-containing mouthwash. Two brands of alcohol-containing mouthwash and their alcohol-free counterparts were used to treat two oral cell lines derived from normal (OKF6-TERT) and dysplastic (DOK) tissues. Genotoxicity was determined by Comet assay. RNA-seq was performed using the Ion Torrent platform. Bioinformatics analysis used R/Bioconductor packages with differential expression using DEseq2. Pathway enrichment analysis used EnrichR with the WikiPathways and Kegg databases. Both cell lines displayed dose-dependent DNA damage in response to acute exposure to ethanol and alcohol-containing mouthwashes as well as alcohol-free mouthwashes reconstituted with ethanol as shown by Comet assay. The transcriptomic effects of alcohol-containing mouthwash exposure were more complex with significant differential gene expression ranging from >2000 genes in dysplastic (DOK) cells to <100 genes in normal (OKF6-TERT) cells. Pathway enrichment analysis in DOK cells revealed alcohol-containing mouthwashes showed common features between the two brands used including DNA damage response as well as cancer-associated pathways. In OKF6-TERT cells, the most significantly enriched pathways involved inflammatory signalling. Alcohol-containing mouthwashes are genotoxic in vitro to normal and dysplastic oral keratinocytes and induce widespread changes in gene expression. Dysplastic cells are more susceptible to the transcriptomic effects of mouthwash. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.

PubMed

Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun

2018-05-01

Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Using media exposure to predict the initiation and persistence of youth alcohol use in Taiwan.

PubMed

Chang, Fong-ching; Lee, Ching-mei; Chen, Ping-hung; Chiu, Chiung-hui; Miao, Nae-fang; Pan, Yun-chieh; Huang, Tzu-fu; Lee, Shu-ching

2014-05-01

Youth consumption of alcohol is a major public health problem in Taiwan, yet little research has been conducted to examine the potential influence of exposure to alcohol advertising. The present study examined the prospective influence that exposure to alcohol advertising has on the initiation and persistence of youthful drinking in Taiwan. A total of 2315 students from 26 high schools in Taipei, Taiwan were assessed in the 10th grade with follow-up conducted in the 11th grade. Self-administered questionnaires were collected in 2010 and 2011 to assess the patterns of change in youth alcohol drinking behaviors, media exposure to alcohol, and risk and protective factors. Of the 1712 non-drinking students in the 10th grade, 285 (16.6%) had initiated drinking by the 11th grade. Of the 590 drinkers in the 10th grade, 396 (67.1%) were persistently drinking by the 11th grade. Multivariate analysis results indicated that when other potential confounders were accounted for, greater media exposure to alcohol advertising in the 10th grade was found to be significantly associated with the initiation of alcohol use and when combined with an increase in media exposure from grades 10 to 11, this was significantly associated with the persistence of alcohol use. Exposure to alcohol advertising in the media was associated with both the initiation and the persistence of alcohol use by youth. Copyright © 2014 Elsevier B.V. All rights reserved.

Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure

PubMed Central

Panczakiewicz, Amy L.; Glass, Leila; Coles, Claire D.; Kable, Julie A.; Sowell, Elizabeth R.; Wozniak, Jeffrey R.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

2016-01-01

Background Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented, however the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Methods Subjects were 407 youth with prenatal alcohol exposure (n=192) and controls (n=215). Two age groups [child (5–7y) or adolescent (10–16y)] and both sexes were included. All subjects completed standardized neuropsychological testing and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) MANOVAs. Significant effects were followed by univariate analyses. Results No three-way or two-way interactions were significant. The main effect of group was significant in all three MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on three measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual-spatial scores and fewer somatic complaints than females. Conclusion Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for non-exposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by

Interhemispheric Functional Brain Connectivity in Neonates with Prenatal Alcohol Exposure: Preliminary Findings.

PubMed

Donald, Kirsten A; Ipser, Jonathan C; Howells, Fleur M; Roos, Annerine; Fouche, Jean-Paul; Riley, Edward P; Koen, Nastassja; Woods, Roger P; Biswal, Bharat; Zar, Heather J; Narr, Katherine L; Stein, Dan J

2016-01-01

Children exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored. Sixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed (PAE) and 14 age-matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit. Alcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance. Although results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children. Copyright © 2016 by the Research Society on Alcoholism.

Gaze‐evoked nystagmus induced by alcohol intoxication

PubMed Central

Tarnutzer, Alexander A.; Straumann, Dominik; Ramat, Stefano; Bertolini, Giovanni

2017-01-01

Key points The cerebellum is the core structure controlling gaze stability. Chronic cerebellar diseases and acute alcohol intoxication affect cerebellar function, inducing, among others, gaze instability as gaze‐evoked nystagmus.Gaze‐evoked nystagmus is characterized by increased centripetal eye‐drift. It is used as an important diagnostic sign for patients with cerebellar degeneration and to assess the ‘driving while intoxicated’ condition.We quantified the effect of alcohol on gaze‐holding using an approach allowing, for the first time, the comparison of deficits induced by alcohol intoxication and cerebellar degeneration.Our results showed that alcohol intoxication induces a two‐fold increase of centripetal eye‐drift.We establish analysis techniques for using controlled alcohol intake as a model to support the study of cerebellar deficits.The observed similarity between the effect of alcohol and the clinical signs observed in cerebellar patients suggests a possible pathomechanism for gaze‐holding deficits. Abstract Gaze‐evoked nystagmus (GEN) is an ocular‐motor finding commonly observed in cerebellar disease, characterized by increased centripetal eye‐drift with centrifugal correcting saccades at eccentric gaze. With cerebellar degeneration being a rare and clinically heterogeneous disease, data from patients are limited. We hypothesized that a transient inhibition of cerebellar function by defined amounts of alcohol may provide a suitable model to study gaze‐holding deficits in cerebellar disease. We recorded gaze‐holding at varying horizontal eye positions in 15 healthy participants before and 30 min after alcohol intake required to reach 0.6‰ blood alcohol content (BAC). Changes in ocular‐motor behaviour were quantified measuring eye‐drift velocity as a continuous function of gaze eccentricity over a large range (±40 deg) of horizontal gaze angles and characterized using a two‐parameter tangent model. The effect of

Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone

PubMed Central

Besheer, Joyce; Fisher, Kristen R.; Lindsay, Tessa G.; Cannady, Reginald

2013-01-01

Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5–0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals. PMID:23643750

Prenatal alcohol exposure and cellular differentiation: a role for Polycomb and Trithorax group proteins in FAS phenotypes?

PubMed

Veazey, Kylee J; Muller, Daria; Golding, Michael C

2013-01-01

Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell-cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell's identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes--the Polycomb and Trithorax proteins--are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

PubMed Central

Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure. PMID:25960751

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

PubMed

Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Simple exposure to alcohol cues causally increases negative implicit attitudes toward lesbians and gay men.

PubMed

Greitemeyer, Tobias; Nierula, Carina

2016-01-01

Previous research has shown that acute alcohol consumption is associated with negative responses toward outgroup members such as sexual minorities. However, simple alcohol cue exposure without actually consuming alcohol also influences social behavior. Hence, it was reasoned that priming participants with words related to alcohol (relative to neutral words) would promote prejudiced attitudes toward sexual minorities. In fact, an experiment showed that alcohol cue exposure causally led to more negative implicit attitudes toward lesbians and gay men. In contrast, participants' explicit attitudes were relatively unaffected by the priming manipulation. Moreover, participants' typical alcohol use was not related to their attitudes toward lesbians and gay men. In sum, it appears that not only acute alcohol consumption but also the simple exposure of alcohol cues may promote negative views toward lesbians and gay men.

Youth exposure to alcohol advertising in magazines--United States, 2001-2005.

PubMed

2007-08-03

Alcohol consumption among persons aged 12-20 years contributes to the three leading causes of death (unintentional injury, homicide, and suicide) in this age group in the United States and is associated with other health-risk behaviors, including high-risk sexual activity, smoking, and physical fighting. Recent studies have documented the contribution of alcohol marketing to underage drinking. In 2000, the trade association for the wine industry changed its voluntary marketing code to stop advertising in magazines in which youths aged 12-20 years were >30% of the audience. In 2003, this threshold was adopted by the trade associations for beer and liquor producers. To determine the proportion of alcohol advertisements placed in magazines with disproportionately large youth readerships (i.e., >15% of readers aged 12-20 years) and to assess the proportion of youths exposed to these advertisements, the Center on Alcohol Marketing and Youth (Health Policy Institute, Georgetown University, District of Columbia) evaluated the placement of alcohol advertisements in 143 national magazines for which readership composition data were available for 2001-2005; these 143 publications accounted for approximately 90% of expenditures for all alcohol advertising in national print magazines. This report summarizes the results of that study, which indicated that alcohol advertising remained common in magazines with >15% youth readership but decreased substantially in magazines with >30% youth readership. These results suggest that although voluntary industry standards have reduced youth exposure to alcohol advertising in magazines, strengthening these standards by establishing a >15% youth readership threshold would further reduce exposure. In addition, independent monitoring of youth exposure to alcohol advertising should continue, as recommended by the U.S. Congress and Surgeon General.

Television and music video exposure and risk of adolescent alcohol use.

PubMed

Robinson, T N; Chen, H L; Killen, J D

1998-11-01

Alcohol use is frequently portrayed in television programming and advertising. Exposure to media portrayals of alcohol use may lead to increased drinking. To address this issue, we examined prospectively the associations between media exposure and alcohol use in adolescents. Prospective cohort study. Setting. Six public high schools in San Jose, California. Participants. Ninth-grade students (N = 1533; mean age = 14.6 years). Students reported hours of television, music video, and videotape viewing; computer and video game use; and lifetime and past 30 days' alcohol use at baseline and 18 months later. Associations between baseline media exposure and subsequent alcohol use were examined with multiple logistic regression. During the 18-month follow-up, 36.2% of baseline nondrinkers began drinking and 50.7% of baseline drinkers continued to drink. Onset of drinking was significantly associated with baseline hours of television viewing (odds ratio [OR] = 1.09; 95% confidence interval [95% CI] = 1.01-1.18), music video viewing (OR = 1.31; 95% CI = 1. 17-1.47), and videotape viewing (OR = 0.89; 95% CI = 0.79-0.99), controlling for age, sex, ethnicity, and other media use. Computer and video game use was not significantly associated with the subsequent onset of drinking. Among baseline drinkers, there were no significant associations between baseline media use and maintenance of drinking. Increased television and music video viewing are risk factors for the onset of alcohol use in adolescents. Attempts to prevent adolescent alcohol use should address the adverse influences of alcohol use in the media.

Exposure to Alcohol Use in Motion Pictures and Teen Drinking in Latin America.

PubMed

Mejia, Raul; Pérez, Adriana; Abad-Vivero, Erika N; Kollath-Cattano, Christy; Barrientos-Gutierrez, Inti; Thrasher, James F; Sargent, James D

2016-03-01

Our objective was to assess whether exposure to alcohol use in films (AUF) is associated with alcohol use susceptibility, current alcohol use, and binge drinking in adolescents from 2 Latin American countries. We performed a cross-sectional study with 13,295 middle school students from public and private schools in Mexico and Argentina. Exposure to alcohol use in over 400 contemporary top box office films in each country was estimated using previously validated methods. Outcome measures included current drinking (i.e., any drink in the last 30 days), ever binge drinking (i.e., more than 4 or 5 drinks in a row for females and males, respectively) and, among never drinkers, alcohol susceptibility (i.e., might drink in the next year or accept a drink from a friend). Multivariate models were adjusted for age, sex, parental education, peer drinking, sensation seeking, parenting style, and media access. Mean age was 12.5 years (SD = 0.7), and the prevalence of alcohol consumption and binge drinking was 19.8 and 10.9%, respectively. Mean exposure to alcohol from the film sample was about 7 hours in both countries. Adjusted models indicated independent dose-response associations between higher levels of exposure to AUF and all outcomes; the adjusted odds ratios (aORs) comparing quartiles 4 and 1, 1.99 (95% confidence interval [CI] 1.73 to 2.30) for current drinking, aOR 1.68 (CI 1.39 to 2.02) for binge drinking, and aOR 1.80 (1.52 to 2.12) for alcohol susceptibility. Compared to Mexican adolescents, Argentine adolescents were significantly more likely to have engaged in binge drinking (aOR 1.40, 95% CI 1.12 to 1.76) and, among never drinkers, were more susceptible to try drinking (aOR 1.40, 95% CI 1.20 to 1.64). Higher levels of exposure to AUF were associated with higher likelihood of alcohol use, binge drinking, and alcohol susceptibility in Latin American adolescents. Copyright © 2016 by the Research Society on Alcoholism.

Exposure to alcohol use in motion pictures and teen drinking in Latin America

PubMed Central

Mejia, Raul; Pérez, Adriana; Abad-Vivero, Erika N.; Kollath-Cattano, Christy; Gutierrez, Inti Barrientos; Thrasher, James F.; Sargent, James D.

2015-01-01

Objectives To assess whether exposure to alcohol use in films (AUF) is associated with alcohol use susceptibility, current alcohol use, and binge drinking in adolescents from two Latin American countries. Methods Cross-sectional study with 13,295 middle school students from public and private schools in Mexico and Argentina. Exposure to alcohol use in over 400 contemporary top box office films in each country was estimated using previously validated methods. Outcome measures included current drinking (i.e., any drink in the last 30 days), ever binge-drinking (i.e., more than 4 or 5 drinks in a row for females and males, respectively) and, among never drinkers, alcohol susceptibility (i.e., might drink in the next year or accept a drink from a friend). Multivariate models were adjusted for age, sex, parental education, peer drinking, sensation seeking, parenting style and media access. Results Mean age was 12.5 years (SD = 0.7) and the prevalence of alcohol consumption and binge drinking was 19.8% and 10.9% respectively. Mean exposure to alcohol from the film sample was about 7 hours in both countries. Adjusted models indicated independent dose-response associations between higher levels of exposure to AUF and all outcomes; the adjusted odds ratios (OR) comparing quartiles 4 and 1 1.99 (95% CI 1.73 - 2.30) for current drinking, 1.68 (1.39 - 2.02) for binge drinking, and 1.80 (1.52 - 2.12) for alcohol susceptibility. Compared to Mexican adolescents, Argentine adolescents were significantly more likely to have engaged in binge drinking (OR 1.40, 95% CI 1.12 - 1.76.) and, among never drinkers, were more susceptible to trying drinking (OR 1.40, 95% CI 1.20 - 1.64). Conclusions Higher levels of exposure to alcohol use in films was associated with higher likelihood of alcohol use, binge drinking, and alcohol susceptibility in Latin American adolescents. PMID:26857804

Youth exposure to alcohol advertising on television--25 markets, United States, 2010.

PubMed

2013-11-08

Excessive alcohol consumption accounted for an estimated 4,700 deaths and 280,000 years of potential life lost among youths aged <21 years each year during 2001-2005. Exposure to alcohol marketing increases the likelihood to varying degrees that youths will initiate drinking and drink at higher levels. By 2003, the alcohol industry voluntarily agreed not to advertise on television programs where >30% of the audience is reasonably expected to be aged <21 years. However, the National Research Council/Institute of Medicine (NRC/IOM) proposed in 2003 that "the industry standard should move toward a 15% threshold for television advertising". Because local media markets might have different age distributions, the Center on Alcohol Marketing and Youth, Johns Hopkins Bloomberg School of Public Health, evaluated the proportion of advertisements that appeared on television programs in 25 local television markets* and resulting youth exposure that exceeded the industry standard (i.e., >30% aged 2-20 years) or the proposed NRC/IOM standard (i.e., >15% aged 12-20 years). Among national television programs with alcohol advertising, placements were assessed for the 10 programs with the largest number of youth viewers within each of four program categories: network sports, network nonsports, cable sports, and cable nonsports (40 total). Of the 196,494 alcohol advertisements that aired on television programs with the largest number of youth viewers in these local markets, placement of 23.7% exceeded the industry threshold and 35.4% exceeded the NRC/IOM threshold. These results indicate that the alcohol industry's self-regulation of its advertising could be improved, and youth exposure to alcohol advertising could be further reduced by adopting and complying with the NRC/IOM standard. In addition, continued public health surveillance would allow for sustained assessment of youth exposure to alcohol advertising and inform future interventions.

Evaluation of Furfuryl Alcohol Sensitization Potential Following Dermal and Pulmonary Exposure: Enhancement of Airway Responsiveness

PubMed Central

Franko, Jennifer; Jackson, Laurel G.; Hubbs, Ann; Kashon, Michael; Meade, B. J.; Anderson, Stacey E.

2015-01-01

Furfuryl alcohol is considered by the U.S. Environmental Protection Agency to be a high volume production chemical, with over 1 million pounds produced annually. Due to its high production volume and its numerous industrial and consumer uses, there is considerable potential for work-related exposure, as well as exposure to the general population, through pulmonary, oral, and dermal routes of exposure. Human exposure data report a high incidence of asthma in foundry mold workers exposed to furan resins, suggesting potential immunologic effects. Although furfuryl alcohol was nominated and evaluated for its carcinogenic potential by the National Toxicology Program, studies evaluating its immunotoxicity are lacking. The studies presented here evaluated the immunotoxic potential of furfuryl alcohol following exposure by the dermal and pulmonary routes using a murine model. When tested in a combined irritancy local lymph node assay, furfuryl alcohol was identified to be an irritant and mild sensitizer (EC3 = 25.6%). Pulmonary exposure to 2% furfuryl alcohol resulted in enhanced airway hyperreactivity, eosinophilic infiltration into the lungs, and enhanced cytokine production (IL-4, IL-5, and interferon-γ) by ex vivo stimulated lung-associated draining lymphoid cells. Airway hyperreactivity and eosinophilic lung infiltration were augmented by prior dermal exposure to furfuryl alcohol. These results suggest that furfuryl alcohol may play a role in the development of allergic airway disease and encourage the need for additional investigation. PMID:22003193

Mechanisms of Enhanced Hemoglobin Electroactivity on Carbon Electrodes upon Exposure to a Water-Miscible Primary Alcohol.

PubMed

Tom, Justin; Jakubec, Philip J; Andreas, Heather A

2018-05-01

Exposing a carbon electrode to hemoglobin (Hb) and alcoholic solvents, such as methanol, ethanol or 1-propanol, drastically changes Hb electroactivity, but until this work, the important underlying mechanisms were unclear. For the first time, we show that these alcohols impact Hb electroactivity via three mechanisms: modification of the carbon surface oxides on the glassy carbon (GC) electrode, Hb film formation, and structural changes to Hb. C 1s X-ray photoelectron spectroscopy provided evidence for significant alcohol-induced modification of the carbon surface oxides, and differential pulse voltammetry showed links between these modifications and Hb electroactivity. Spectroscopic ellipsometry showed that Hb films formed during exposure to Hb- and alcohol-containing electrolytes increased in thickness with increasing alcohol content, although film thickness played only a minor role in Hb electroactivity. Alcohol-induced structural changes in Hb are confirmed with UV-visible absorption and fluorescence data, showing that Hb denaturation also was a significant factor in increasing Hb electroactivity. Carbon-surface-oxide modification and Hb denaturation worked in tandem to maximally increase the Hb electroactivity in 60% methanol. While in ethanol and 1-propanol, the significant increases in Hb electroactivity caused by Hb denaturation were offset by an increase in Hb-inhibiting carbon surface oxides. Knowledge of these mechanisms shows the impact of alcohols on both Hb and carbon electrodes, allows for thoughtful design of the Hb-sensing system, is vital for proper analysis of Hb electroactivity in the presence of these alcohols (e.g., when used as binder solvents for immobilizing Hb into films), and provides fundamental understanding of the Hb-carbon interactions.

Sleep in infants and children with prenatal alcohol exposure.

PubMed

Inkelis, Sarah M; Thomas, Jennifer D

2018-05-31

Prenatal exposure to alcohol can result in a range of neurobehavioral impairments and physical abnormalities. The term fetal alcohol spectrum disorders (FASD) encompasses the outcomes of prenatal alcohol exposure (PAE), the most severe of which is fetal alcohol syndrome (FAS). These effects have lifelong consequences, placing a significant burden on affected individuals, caregivers, and communities. Caregivers of affected children often report that their child has sleep problems, and many symptoms of sleep deprivation overlap with the cognitive and behavioral deficits characteristic of FASD. Alcohol-exposed infants and children demonstrate poor sleep quality based on measures of electroencephalography (EEG), actigraphy, and questionnaires. These sleep studies indicate a common theme of disrupted sleep pattern, more frequent awakenings, and reduced total sleep time. However, relatively little is known about circadian rhythm disruption, and the neurobehavioral correlates of sleep disturbance in individuals with PAE. Furthermore, there is limited information available to healthcare providers about identification and treatment of sleep disorders in patients with FASD. This review consolidates the findings from studies of infant and pediatric sleep in this population, providing an overview of typical sleep characteristics, neurobehavioral correlates of sleep disruption, and potential avenues for intervention in the context of PAE. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Children's exposure to alcohol marketing within supermarkets: An objective analysis using GPS technology and wearable cameras.

PubMed

Chambers, T; Pearson, A L; Stanley, J; Smith, M; Barr, M; Ni Mhurchu, C; Signal, L

2017-07-01

Exposure to alcohol marketing within alcohol retailers has been associated with higher rates of childhood drinking, brand recognition, and marketing recall. This study aimed to objectively measure children's everyday exposure to alcohol marketing within supermarkets. Children aged 11-13 (n = 167) each wore a wearable camera and GPS device for four consecutive days. Micro-spatial analyses were used to examine exposures within supermarkets. In alcohol retailing supermarkets (n = 30), children encountered alcohol marketing on 85% of their visits (n = 78). Alcohol marketing was frequently near everyday goods (bread and milk) or entrance/exit. Alcohol sales in supermarkets should be banned in order to protect children from alcohol marketing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cross-Lagged Associations Between Substance Use-Related Media Exposure and Alcohol Use During Middle School

PubMed Central

Tucker, Joan S.; Miles, Jeremy N. V.; D’Amico, Elizabeth J.

2013-01-01

Purpose This study examines the reciprocal longitudinal associations between alcohol or other drug (AOD)-related media exposure and alcohol use among middle school students, and explores whether these associations differ by ethnicity or gender. Methods The analytic sample is 7th grade students who were recruited from 16 California middle schools and surveyed in the spring semester of two academic years. Students reported on their background characteristics, exposure to seven types of AOD-related media content (internet videos, social networking sites, movies, television, magazine advertisements, songs, and video games) in the past 3 months, and alcohol use in the past 30 days. Structural equation modeling was used to examine cross-lagged associations between media exposure and alcohol use. Results Greater AOD-related media exposure in 7th grade was significantly associated with a higher probability of alcohol use in 8th grade (p=.02), and alcohol use in 7th grade was marginally associated with greater AOD-related media exposure in 8th grade (p=.07). These cross-lagged associations did not statistically differ by ethnicity (Hispanic vs. non-Hispanic white) or gender. Further, there was no evidence that certain types of media exposure were more strongly associated with alcohol use than others. Conclusions Results from this study suggest that AOD-related media effects and media selectively form a reciprocal, mutually influencing process that may escalate adolescent alcohol use over time. Addressing adolescents’ exposure to AOD-related media content and its effects on behavior, such as through media literacy education, may hold promise for improving the efficacy of alcohol prevention efforts for middle school students. PMID:23770074

Cross-lagged associations between substance use-related media exposure and alcohol use during middle school.

PubMed

Tucker, Joan S; Miles, Jeremy N V; D'Amico, Elizabeth J

2013-10-01

This study examines the reciprocal longitudinal associations between alcohol or other drug (AOD)-related media exposure and alcohol use among middle school students, and explores whether these associations differ by ethnicity or gender. The analytic sample is 7th grade students who were recruited from 16 California middle schools and surveyed in the spring semester of two academic years. Students reported on their background characteristics, exposure to seven types of AOD-related media content (Internet videos, social networking sites, movies, television, magazine advertisements, songs, and video games) in the past 3 months, and alcohol use in the past 30 days. Structural equation modeling was used to examine cross-lagged associations between media exposure and alcohol use. Greater AOD-related media exposure in 7th grade was significantly associated with a higher probability of alcohol use in 8th grade (p = .02), and alcohol use in 7th grade was marginally associated with greater AOD-related media exposure in 8th grade (p = .07). These cross-lagged associations did not statistically differ by ethnicity (Hispanic vs. non-Hispanic white) or gender. Further, there was no evidence that certain types of media exposure were more strongly associated with alcohol use than others. Results from this study suggest that AOD-related media effects and media selectively form a reciprocal, mutually influencing process that may escalate adolescent alcohol use over time. Addressing adolescents' exposure to AOD-related media content and its effects on behavior, such as through media literacy education, may hold promise for improving the efficacy of alcohol prevention efforts for middle school students. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Pre-implantation alcohol exposure and developmental programming of FASD: an epigenetic perspective.

PubMed

Legault, Lisa-Marie; Bertrand-Lehouillier, Virginie; McGraw, Serge

2018-04-01

Exposure to alcohol during in-utero development can permanently change the developmental programming of physiological responses, thereby increasing the risk of neurological illnesses during childhood and later adverse health outcomes associated with fetal alcohol spectrum disorder (FASD). There is an increasing body of evidence indicating that exposure to alcohol during gestation triggers lasting epigenetic alterations in offspring, long after the initial insult; together, these studies support the role of epigenetics in FASD etiology. However, we still have little information about how ethanol interferes with the fundamental epigenetic reprogramming wave (e.g., erasure and re-establishment of DNA methylation marks) that characterizes pre-implantation embryo development. This review examines key epigenetic processes that occur during pre-implantation development and especially focus on the current knowledge regarding how prenatal exposure to alcohol during this period could affect the developmental programming of the early stage pre-implantation embryo. We will also outline the current limitations of studies examining the in-vivo and in-vitro effects of alcohol exposure on embryos and underline the next critical steps to be taken if we want to better understand the implicated mechanisms to strengthen the translational potential for epigenetic markers for non-invasive early detection, and the treatment of newborns that have higher risk of developing FASD.

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

PubMed

Treit, Sarah; Zhou, Dongming; Chudley, Albert E; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

2016-01-01

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure

PubMed Central

Treit, Sarah; Zhou, Dongming; Chudley, Albert E.; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M.; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

2016-01-01

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5–19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol

The effects of xenon and nitrous oxide gases on alcohol relapse.

PubMed

Vengeliene, Valentina; Bessiere, Baptiste; Pype, Jan; Spanagel, Rainer

2014-02-01

In recent years, the glutamate theory of alcoholism has emerged as a major theory in the addiction research field and N-methyl-d-aspartate (NMDA) receptors have been shown to play a major role in alcohol craving and relapse. The NMDA receptors are considered as the primary side of action of the anesthetic gases xenon (Xe) and nitrous oxide (N2 O). Despite the rapid on/off kinetics of these gases on the NMDA receptor, a brief gas exposure can induce an analgesic or antireward effect lasting several days. The aim of this study was to examine the effect of both Xe and N2 O on alcohol-seeking and relapse-like drinking behavior (measured as the alcohol deprivation effect) in Wistar rats. We used 2 standard procedures-the alcohol deprivation model with repeated deprivation phases and the cue-induced reinstatement model of alcohol seeking-to study the effect of 2 brief gas exposures of either Xe, N2 O, or control gas on relapse-like drinking and alcohol-seeking behavior. Here, we show that exposure to Xe during the last 24 hours of abstinence produced a trend toward reduced ethanol intake during the first alcohol re-exposure days. In addition, Xe gas exposure significantly decreased the cue-induced reinstatement of alcohol-seeking behavior. N2 O had no effect on either behavior. Xe reduces alcohol-seeking behavior in rats and may therefore also interfere with craving in human alcoholics. Copyright © 2013 by the Research Society on Alcoholism.

Exposure to Online Alcohol Marketing and Adolescents' Drinking: A Cross-sectional Study in Four European Countries.

PubMed

de Bruijn, Avalon; Engels, Rutger; Anderson, Peter; Bujalski, Michal; Gosselt, Jordy; Schreckenberg, Dirk; Wohtge, Jördis; de Leeuw, Rebecca

2016-09-01

The Internet is the leading medium among European adolescents in contemporary times; even more time is spent on the Internet than watching television. This study investigates associations between online alcohol marketing exposure and onset of drinking and binge drinking among adolescents in four European countries. A total of 9038 students with a mean age of 14.05 (SD 0.82) participated in a school-based survey in Germany, Italy, the Netherlands and Poland. Logistic regression analyses of cross-sectional cross-country survey data were undertaken. Exposure to online alcohol marketing, televised alcohol advertising and ownership of alcohol-branded items was estimated to be controlled for relevant confounders. Onset of drinking and binge drinking in the past 30 days were included in the study as outcome variables. Adjusted for relevant confounders, higher exposure to (online) alcohol marketing exposure was found to be related to the odds of starting to drink (p < 0.001) and the odds of binge drinking in the past 30 days (p < 0.001). This effect was found to be consistent in all four countries. Active engagement with online alcohol marketing was found to interact more strongly with drinking outcomes than passive exposure to online alcohol marketing. Youngsters in the four European countries report frequent exposure to online alcohol marketing. The association between this exposure and adolescents' drinking was robust and seems consistent across national contexts. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Perinatal alcohol exposure enhances nocistatin levels in adulthood.

PubMed

Tekes, Kornélia; Hantos, Mónika; Gyenge, Melinda; Csaba, Gyorgy

2007-06-01

In earlier experiments perinatal hormonal imprinting by alcohol decreased the hormone content of immune cells for life. In the present study, both a single day (15% on the third postnatal day) and a long-term treatment schedule of alcohol exposure (3% for 21 days) of dams during lactation significantly (P < 0.01) enhanced endogenous levels of nocistatin in the blood plasma as well as in the cerebrospinal fluid of the offspring, measured in 3-month-old rats. Our data suggest that alcohol consumption during lactation can cause a life-long influence on nocistatin levels in the offspring and most likely modify nocistatin-related functions such as pain tolerance.

Measuring youth exposure to alcohol marketing on social networking sites: challenges and prospects.

PubMed

Jernigan, David H; Rushman, Anne E

2014-02-01

Youth exposure to alcohol marketing has been linked to increased alcohol consumption and problems. On relatively new and highly interactive social networking sites (SNS) that are popular with youth, tools for measuring youth exposure to alcohol marketing in traditional media are inadequate. We critically review the existing policies of Facebook, Twitter, and YouTube designed to keep branded alcohol content away from underage youth. Looking at brand and user activity on Facebook for the 15 alcohol brands most popular among US youth, we found activity has grown dramatically in the past 3 years, and underage users may be accounting for some of this activity. Surveys of youth and adult participation in alcohol marketing on SNS will be needed to inform debate over these marketing practices.

Lifelong Impacts of Moderate Prenatal Alcohol Exposure on Neuroimmune Function

PubMed Central

Noor, Shahani; Milligan, Erin D.

2018-01-01

In utero alcohol exposure is emerging as a major risk factor for lifelong aberrant neuroimmune function. Fetal alcohol spectrum disorder encompasses a range of behavioral and physiological sequelae that may occur throughout life and includes cognitive developmental disabilities as well as disease susceptibility related to aberrant immune and neuroimmune actions. Emerging data from clinical studies and findings from animal models support that very low to moderate levels of fetal alcohol exposure may reprogram the developing central nervous system leading to altered neuroimmune and neuroglial signaling during adulthood. In this review, we will focus on the consequences of low to moderate prenatal alcohol exposure (PAE) on neuroimmune interactions during early life and at different stages of adulthood. Data discussed here will include recent studies suggesting that while abnormal immune function is generally minimal under basal conditions, following pathogenic stimuli or trauma, significant alterations in the neuroimmune axis occur. Evidence from published reports will be discussed with a focus on observations that PAE may bias later-life peripheral immune responses toward a proinflammatory phenotype. The propensity for proinflammatory responses to challenges in adulthood may ultimately shape neuron–glial-immune processes suspected to underlie various neuropathological outcomes including chronic pain and cognitive impairment.

Sex-specific effects of developmental alcohol exposure on cocaine-induced place preference in adulthood.

PubMed

Macht, Victoria A; Kelly, Sandra J; Gass, Justin T

2017-08-14

Fetal Alcohol Syndrome (FAS) is associated with high rates of drug addiction in adulthood. One possible basis for increased drug use in this population is altered sensitivity to drug-associated contexts. This experiment utilized a rat model of FASD to examine behavioral and neural changes in the processing of drug cues in adulthood. Alcohol was given by intragastric intubation to pregnant rats throughout gestation and to rat pups during the early postnatal period (ET group). Controls consisted of a non-treated group (NC) and a pair-fed group given the intubation procedure without alcohol (IC). On postnatal day (PD) 90, rats from all treatment groups were given saline, 0.3mg/kg, 3.0mg/kg, or 10.0mg/kg cocaine pairings with a specific context in the conditioned place preference (CPP) paradigm. While control animals of both sexes showed cocaine CPP at the 3.0 and 10.0mg/kg doses, ET females also showed cocaine CPP at 0.3mg/kg. This was accompanied by a decrease in c-Fos/GAD 67 cells in the nucleus accumbens (NAc) shell and GAD 67 -only cells in the NAc shell and PFC at this 0.3mg/kg dose. ET males failed to show cocaine CPP at the 3.0mg/kg dose. This was associated with an increase in c-Fos only-labeled cells in the NAc core and PFC at this 3.0mg/kg dose. These results suggest that developmental alcohol exposure has a sexually-dimorphic effect on cocaine's conditioning effects in adulthood and the NAc. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of tobacco smoke exposure on pharmacokinetics of ethyl alcohol in alcohol preferring and non-preferring rats.

PubMed

Florek, Ewa; Kulza, Maksymilian; Piekoszewski, Wojciech; Gomółka, Ewa; Jawień, Wojciech; Teżyk, Artur; Napierała, Marta

2015-10-01

A vast majority of people who abuse alcohol are also defined as "heavy smokers". Tobacco smokes induces CYP1A1, CYP1A2, CYP2A6 isoenzymes, but on the other hand, ethanol activates CYP2E1, which can be important during combined, chronic use of both of them. The aim of the study was to evaluate the influence of tobacco smoke xenobiotics on ethanol pharmacokinetics and the level of its metabolites in alcohol preferring and non-preferring rats. Ethanol, acetaldehyde, methanol, n-propanol and n-butanol were determined in whole blood by means of gas chromatography. Cotinine in serum was determined by LC-MS/MS. A non-compartmental analysis (cotinine, acetaldehyde) and Widmark equation (ethanol) were used for pharmacokinetic parameters calculation. Ethanol levels were lower in animals exposed to tobacco smoke compared to rats receiving this xenobiotic, without a prior exposure to tobacco smoke. Lower values of the studied pharmacokinetic parameters were observed in the alcohol preferring males compared to the non-alcohol preferring rats. Both n-propanol and n-butanol had higher values of the pharmacokinetic parameters analyzed in the animals exposed to tobacco smoke and ethanol compared to those, which ethanol was administered only once. An increase in maximum concentration and the area under concentration-time curve for ethanol after its administration to rats preferring alcohol and exposed to tobacco smoke are accompanied by a decrease in the volume of distribution. The changes in the volume of distribution may be caused by an increase in the first-pass effect, in the intestinal tract and/or in the liver. The acetaldehyde elimination rate constant was significantly higher in alcohol-preferring animals. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Prenatal Exposure to Drugs/Alcohol: Characteristics and Educational Implications of Fetal Alcohol Syndrome and Cocaine/Polydrug Effects.

ERIC Educational Resources Information Center

Soby, Jeanette M.

This book presents the characteristics of children affected by prenatal drug exposure, fetal alcohol syndrome, fetal alcohol effects, and fetal cocaine/polydrug effects. It outlines incidence, service needs, prevention, and identification. The medical literature on the physical, cognitive, and behavioral characteristics of this population is…

Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure

PubMed Central

Balaraman, Sridevi; Idrus, Nirelia M.; Miranda, Rajesh C.; Thomas, Jennifer D.

2017-01-01

Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol’s developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol’s long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4–9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4–21. On PD 22, subjects were sacrificed, and RNA isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was normalized with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p<0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p<0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by

Social Information Processing Skills in Children with Histories of Heavy Prenatal Alcohol Exposure

ERIC Educational Resources Information Center

McGee, Christie L.; Bjorkquist, Olivia A.; Price, Joseph M.; Mattson, Sarah N.; Riley, Edward P.

2009-01-01

Based on caregiver report, children with prenatal alcohol exposure have difficulty with social functioning, but little is known about their social cognition. The current study assessed the social information processing patterns of school-age children with heavy prenatal alcohol exposure using a paradigm based on Crick and Dodge's reformulated…

Alcohol exposure differentially effects anti-tumor immunity in females by altering dendritic cell function.

PubMed

Thompson, Matthew G; Navarro, Flor; Chitsike, Lennox; Ramirez, Luis; Kovacs, Elizabeth J; Watkins, Stephanie K

2016-12-01

Dendritic cells (DCs) are a critical component of anti-tumor immunity due to their ability to induce a robust immune response to antigen (Ag). Alcohol was previously shown to reduce DC ability to present foreign Ag and promote pro-inflammatory responses in situations of infection and trauma. However the impact of alcohol exposure on generation of an anti-tumor response, especially in the context of generation of an immune vaccine has not been examined. In the clinic, DC vaccines are typically generated from autologous blood, therefore prior exposure to substances such as alcohol may be a critical factor to consider regarding the effectiveness in generating an immune response. In this study, we demonstrate for the first time that ethanol differentially affects DC and tumor Ag-specific T cell responses depending on sex. Signaling pathways were found to be differentially regulated in DC in females compared to males and these differences were exacerbated by ethanol treatment. DC from female mice treated with ethanol were unable to activate Ag-specific cytotoxic T cells (CTL) as shown by reduced expression of CD44, CD69, and decreased production of granzyme B and IFNγ. Furthermore, although FOXO3, an immune suppressive mediator of DC function, was found to be upregulated in DC from female mice, ethanol related suppression was independent of FOXO3. These findings demonstrate for the first time differential impacts of alcohol on the immune system of females compared to males and may be a critical consideration for determining the effectiveness of an immune based therapy for cancer in patients that consume alcohol. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Adolescents' exposure to paid alcohol advertising on television and their alcohol use: exploring associations during a 13-year period.

PubMed

White, Victoria; Azar, Denise; Faulkner, Agatha; Coomber, Kerri; Durkin, Sarah; Livingston, Michael; Chikritzhs, Tanya; Room, Robin; Wakefield, Melanie

2017-10-01

To determine (i) whether Australian adolescents' exposure to television alcohol advertisements changed between 1999 and 2011 and (ii) examine the association between television alcohol advertising and adolescent drinking behaviours. Cross-sectional surveys conducted every 3 years between 1999 and 2011. Analyses examined associations between advertising exposures and reported drinking. Five Australian major cities. Students aged 12-17 years participating in a triennial nationally representative school-based survey residing in the television advertising markets associated with the major cities (sample size range per survey: 12 644-16 004). Outcome measures were: drinking in the past month, past week and past-week risky drinking (5+ drinks on a day). The key predictor variable was past-month adolescent-directed alcohol advertising Targeted Rating Points (TRPs, a measure of television advertising exposure). Control measures included student-level characteristics, government alcohol-control advertising TRPs, road safety (drink-driving) TRPs and time of survey. Average monthly adolescent alcohol TRPs increased between 1999 (mean = 2371) to 2005 (mean = 2679) (P < 0.01) then decreased between 2005 and 2011: (mean = 880) (P < 0.01). Multi-level logistic regression analyses that adjusted for survey timing, student level factors and alcohol-control advertising variables showed a significant association between past-month alcohol TRPs and past-month drinking [odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.07-1.15), past-week drinking (OR = 1.10, 95% CI = 1.06-1.14) and past-week risky drinking (OR = 1.15, 95% CI = 1.09-1.22). Past-week risky drinking was associated inversely with road safety TRPs (OR = 0.69, 95% CI = 0.49-0.98). While Australian adolescents' exposure to alcohol advertising on television reduced between 1999 and 2011, higher levels of past-month television alcohol advertising were associated with an increased likelihood

RE-AIM evaluation of the Alcohol and Pregnancy Project: educational resources to inform health professionals about prenatal alcohol exposure and fetal alcohol spectrum disorder.

PubMed

Payne, Janet M; France, Kathryn E; Henley, Nadine; D'Antoine, Heather A; Bartu, Anne E; O'Leary, Colleen M; Elliott, Elizabeth J; Bower, Carol; Geelhoed, Elizabeth

2011-03-01

The objective was to evaluate the Alcohol and Pregnancy Project that provided health professionals in Western Australia (WA) with educational resources to inform them about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder (FASD). The authors developed, produced, and distributed educational resources to 3,348 health professionals in WA. Six months later, they surveyed 1,483 of these health professionals. The authors used the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance) to evaluate the project. The educational resources were effective in producing a 31% increase in the proportion of health professionals who routinely provided pregnant women with information about the consequences of drinking alcohol during pregnancy. One hundred percent of the settings adopted the project, it reached 96.3% of the target population, it was implemented as intended, and the resources were maintained (http://www.ichr.uwa.edu.au/alcoholandpregnancy). The educational resources for health professionals have potential to contribute to reducing prenatal alcohol exposure and FASD.

Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor based brain morphometry and discriminant analysis

PubMed Central

Sowell, Elizabeth R.; Leow, Alex D.; Bookheimer, Susan Y.; Smith, Lynne M.; O’Connor, Mary J.; Kan, Eric; Rosso, Carly; Houston, Suzanne; Dinov, Ivo D.; Thompson, Paul M.

2010-01-01

Here we investigate the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many who use MA during pregnancy also use alcohol, a known teratogen, we examined whether local brain volumes differed among 61 children (ages 5 to 15), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls (CON group). Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally, and right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and within the MAA group, a negative correlation between full-scale IQ (FSIQ) scores and caudate volume was observed. Limbic structures including the anterior and posterior cingulate, the inferior frontal gyrus (IFG) and ventral and lateral temporal lobes bilaterally were increased in volume in both exposure groups. Further, cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure, and that more severe striatal damage is associated with more severe cognitive deficit. PMID:20237258

Cognitive factors contributing to spelling performance in children with prenatal alcohol exposure.

PubMed

Glass, Leila; Graham, Diana M; Akshoomoff, Natacha; Mattson, Sarah N

2015-11-01

Heavy prenatal alcohol exposure is associated with impaired school functioning. Spelling performance has not been comprehensively evaluated. We examined whether children with heavy prenatal alcohol exposure demonstrate deficits in spelling and related abilities, including reading, and tested whether there are unique underlying mechanisms for observed deficits in this population. Ninety-six school-age children made up 2 groups: children with heavy prenatal alcohol exposure (AE, n = 49) and control children (CON, n = 47). Children completed select subtests from the Wechsler Individual Achievement Test-Second Edition and the NEPSY-II. Group differences and relations between spelling and theoretically related cognitive variables were evaluated using multivariate analysis of variance and Pearson correlations. Hierarchical regression analyses were used to assess contributions of group membership and cognitive variables to spelling performance. The specificity of these deficits and underlying mechanisms was tested by examining the relations between reading ability, group membership, and cognitive variables. Groups differed significantly on all variables. Group membership and phonological processing significantly contributed to spelling performance, whereas for reading, group membership and all cognitive variables contributed significantly. For both reading and spelling, group × working memory interactions revealed that working memory contributed independently only for alcohol-exposed children. Alcohol-exposed children demonstrated a unique pattern of spelling deficits. The relation of working memory to spelling and reading was specific to the AE group, suggesting that if prenatal alcohol exposure is known or suspected, working memory ability should be considered in the development and implementation of explicit instruction. (c) 2015 APA, all rights reserved).

Cognitive Factors Contributing to Spelling Performance in Children with Prenatal Alcohol Exposure

PubMed Central

Glass, Leila; Graham, Diana M.; Akshoomoff, Natacha; Mattson, Sarah N.

2015-01-01

Objective Heavy prenatal alcohol exposure is associated with impaired school functioning. Spelling performance has not been comprehensively evaluated. We examined whether children with heavy prenatal alcohol exposure demonstrate deficits in spelling and related abilities, including reading, and tested whether there are unique underlying mechanisms for observed deficits in this population. Method Ninety-six school-age children comprised two groups: children with heavy prenatal alcohol exposure (AE, n=49) and control children (CON, n=47). Children completed select subtests from the WIAT-II and NEPSY-II. Group differences and relations between spelling and theoretically-related cognitive variables were evaluated using MANOVA and Pearson correlations. Hierarchical regression analyses were utilized to assess contributions of group membership and cognitive variables to spelling performance. The specificity of these deficits and underlying mechanisms was tested by examining the relations between reading ability, group membership, and cognitive variables. Results Groups differed significantly on all variables. Group membership and phonological processing significantly contributed to spelling performance. In addition, a significant group*working memory interaction revealed that working memory independently contributed significantly to spelling only for the AE group. All cognitive variables contributed to reading across groups and a group*working memory interaction revealed that working memory contributed independently to reading only for alcohol-exposed children. Conclusion Alcohol-exposed children demonstrated a unique pattern of spelling deficits. The relation of working memory to spelling and reading was specific to the AE group, suggesting that if prenatal alcohol exposure is known or suspected, working memory ability should be considered in the development and implementation of explicit instruction. PMID:25643217

Thiamin deficiency on fetal brain development with and without prenatal alcohol exposure.

PubMed

Kloss, Olena; Eskin, N A Michael; Suh, Miyoung

2018-04-01

Adequate thiamin levels are crucial for optimal health through maintenance of homeostasis and viability of metabolic enzymes, which require thiamine as a co-factor. Thiamin deficiency occurs during pregnancy when the dietary intake is inadequate or excessive alcohol is consumed. Thiamin deficiency leads to brain dysfunction because thiamin is involved in the synthesis of myelin and neurotransmitters (e.g., acetylcholine, γ-aminobutyric acid, glutamate), and its deficiency increases oxidative stress by decreasing the production of reducing agents. Thiamin deficiency also leads to neural membrane dysfunction, because thiamin is a structural component of mitochondrial and synaptosomal membranes. Similarly, in-utero exposure to alcohol leads to fetal brain dysfunction, resulting in negative effects such as fetal alcohol spectrum disorder (FASD). Thiamin deficiency and prenatal exposure to alcohol could act synergistically to produce negative effects on fetal development; however, this area of research is currently under-studied. This minireview summarizes the evidence for the potential role of thiamin deficiency in fetal brain development, with or without prenatal exposure to alcohol. Such evidence may influence the development of new nutritional strategies for preventing or mitigating the symptoms of FASD.

Low molecular-weight gel fraction of Aloe vera exhibits gastroprotection by inducing matrix metalloproteinase-9 inhibitory activity in alcohol-induced acute gastric lesion tissues.

PubMed

Park, Chul-Hong; Son, Hyeong-U; Yoo, Chi-Yeol; Lee, Sang-Han

2017-12-01

Aloe has been used for the prevention and cure of various diseases and symptoms including burns, injuries, oedema and pain. This study determines the specific inhibitory activity of matrix metalloproteinase (MMP)-9 induced by the low molecular-weight gel fraction of Aloe vera (L.) Burm.f. (lgfAv) on alcohol-induced acute gastric lesions. We examined the protective effects of oral (p.o.) administration of lgfAv (molecular weight cutoff <50.0 kDa, 150.0 mg/kg body weight) in a Balb/c mouse model of alcohol-induced acute gastritis for 1 h exposure. By measuring ulcer index, we compared the antiulcerative activity of the fraction. mRNA expression and immunohistochemical analysis of various biomarkers were performed. The lgfAv-treated mice exhibited drastically fewer ulcer lesions than the untreated control mice did. It featured that lgfAv lessened the ulcer lesions than their relevant controls. Moreover, the transcriptional level of MMP-9 was completely alleviated by lgfAv treatment in alcohol-treated gastritis-induced mice. The transcriptional level of MMP-9 was significantly alleviated by lgfAv treatment of the model. However, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry experiments revealed that lgfAv treatment in mucosal tissues had the potential to inhibit the mRNA and protein expression levels of MMP-9, respectively. The protein expression of MMP-9 was closely associated with lgfAv-induced gastroprotection against alcohol-induced gastric lesions. The present findings suggest that lgfAv has the potential to alleviate alcohol-induced acute gastric lesions, which is mediated in part, mainly by the suppression of the mRNA expression of MMP-9.

Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve male offspring

PubMed Central

Asimes, AnnaDorothea; Torcaso, Audrey; Pinceti, Elena; Kim, Chun K; Zeleznik-Le, Nancy J.; Pak, Toni R.

2016-01-01

Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the last 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring. PMID:27817987

Race, Ethnicity, and Exposure to Alcohol Outlets.

PubMed

Morrison, Christopher; Gruenewald, Paul J; Ponicki, William R

2016-01-01

Prior studies suggest that Black and Hispanic minority populations are exposed to greater concentrations of alcohol outlets, potentially contributing to health disparities between these populations and the White majority. We tested the alternative hypothesis that urban economic systems cause outlets to concentrate in low-income areas and, controlling for these effects, lower demand among minority populations leads to fewer outlets. Market potential for alcohol sales, a surrogate for demand, was estimated from survey and census data across census block groups for 50 California cities. Hierarchical Bayesian conditional autoregressive Poisson models then estimated relationships between observed geographic distributions of outlets and the market potential for alcohol, income, population size, and racial and ethnic composition. Market potentials were significantly smaller among lower income Black, Hispanic, and Asian populations. Block groups with greater market potential and lower income had greater concentrations of outlets. When we controlled for these effects, the racial and ethnic group composition of block groups was mostly unrelated to outlet concentrations. Health disparities related to exposure to alcohol outlets are primarily driven by distributions of income and population density across neighborhoods.

Focused and shifting attention in children with heavy prenatal alcohol exposure.

PubMed

Mattson, Sarah N; Calarco, Katherine E; Lang, Aimée R

2006-05-01

Attention deficits are a hallmark of the teratogenic effects of alcohol. However, characterization of these deficits remains inconclusive. Children with heavy prenatal alcohol exposure and nonexposed controls were evaluated using a paradigm consisting of three conditions: visual focus, auditory focus, and auditory-visual shift of attention. For the focus conditions, participants responded manually to visual or auditory targets. For the shift condition, participants alternated responses between visual targets and auditory targets. For the visual focus condition, alcohol-exposed children had lower accuracy and slower reaction time for all intertarget intervals (ITIs), while on the auditory focus condition, alcohol-exposed children were less accurate but displayed slower reaction time only on the longest ITI. Finally, for the shift condition, the alcohol-exposed group was accurate but had slowed reaction times. These results indicate that children with heavy prenatal alcohol exposure have pervasive deficits in visual focused attention and deficits in maintaining auditory attention over time. However, no deficits were noted in the ability to disengage and reengage attention when required to shift attention between visual and auditory stimuli, although reaction times to shift were slower. Copyright (c) 2006 APA, all rights reserved.

Alcohol Advertising Exposure Among Middle School-Age Youth: An Assessment Across All Media and Venues.

PubMed

Collins, Rebecca L; Martino, Steven C; Kovalchik, Stephanie A; Becker, Kirsten M; Shadel, William G; D'Amico, Elizabeth J

2016-05-01

The purpose of this study was to quantify middle school youth's exposure to alcohol advertisements across media and venues, determine venues of greatest exposure, and identify characteristics of youth who are most exposed. Over a 10-month period in 2013, 589 Los Angeles-area youth ages 11-14 from diverse racial/ethnic backgrounds completed a short paper-and-pencil survey assessing background characteristics and then participated in a 14-day ecological momentary assessment, logging all exposures to alcohol advertisements on handheld computers as they occurred. African American and Hispanic youth were exposed to an average of 4.1 and 3.4 advertisements per day, respectively, nearly two times as many as non-Hispanic White youth, who were exposed to 2.0 advertisements per day. Girls were exposed to 30% more advertisements than boys. Most exposures were to outdoor advertisements, with television advertisements a close second. Exposure to alcohol advertising is frequent among middle school-age youth and may put them at risk for earlier or more frequent underage drinking. Greater restrictions on alcohol advertising outdoors and on television should be considered by regulators and by the alcohol industry and should focus particularly on reducing exposure among minority youth.

Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats

PubMed Central

Yu, Jie; Yang, Xuesong; Luo, Ya; Yang, Xuefeng; Yang, Mengxue; Yang, Jin; Zhou, Jie; Gao, Feng; He, Liting; Xu, Jie

2017-01-01

Endocrine-disrupting chemical (EDC) has been thought to play a role in non-alcoholic fatty liver disease (NAFLD). However, the toxic effects of Nonylphenol (NP), an EDC, on non-alcoholic fatty liver disease have never been elaborated. This study aimed to investigate whether exposure to NP could induce NAFDL, a promoting effect of high-sucrose-high-fat diet (HSHFD) on the adverse effects caused by NP was evaluated. Fourth eight male rats were assigned to four groups and each group was treated with a specific testing sample: normal-diet (ND) control group (C-ND); normal diet plus NP (180mg/kg/day) group (NP-ND); high-sucrose-high-fat-diet control group (C-HSHFD); HSHFD plus NP (180mg/kg/day) group (NP-HSHFD). At the age of 80 day, sonogram presents diffusely increased hepatic echogenicity in the NP-HSHFD group. The oblique diameter of liver in the NP-HSHFD group was significantly bigger than that in both the C-ND and NP-ND groups. At the age of 90 day, exposure to NP-HSHFD and NP-ND caused a significant increase in NP concentration in liver as compared to the C-ND group. The rats in the groups treated with NP+ND, HSHFD and NP+HSHFD produced significant increases in the body weight, fat weight and FMI, respectively, when compared to the C-ND group. The liver weight and hepatosomatic indexes (HIS) of rats in the NP-HSHFD group are higher than those in the C-HSHFD group. Exposure to NP-HSHFD induced the increases in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) as compared to the C-ND group. Morphological examination of liver tissue from rats exposed to NP+HSHFD shown steatosis with marked accumulation of lipid droplets, hepatocellular ballooning degeneration and inflammatory cell infiltration. Chronic exposure to NP might induce NAFLD in male rats. The high-sucrose-high-fat diet accelerates and exacerbates the development of NAFLD caused by NP exposure. PMID:28686624

Middle and High School Students’ Exposure to Alcohol- and Smoking-Related Media: A Pilot Study Using Ecological Momentary Assessment

PubMed Central

Scharf, Deborah M.; Martino, Steven C.; Setodji, Claude M.; Staplefoote, B. Lynette; Shadel, William G.

2013-01-01

The goals of this study were to assess the feasibility of using Ecological Momentary Assessment (EMA) to measure adolescents’ exposure to alcohol and smoking-related media. A sample of 20 middle and high school students completed a two-week EMA protocol in which they monitored exposures to alcohol and smoking-related media. Results showed that adolescents were highly compliant with the study protocol. A total of 255 exposures to alcohol (67%) and smoking (33%) were captured, representing an average of 8.50 (5.82) alcohol-related media exposures and 4.25 (SD = 3.67) smoking-related media exposures and an average of per participant during the study period. Exposures tended to occur in the afternoon (52% alcohol; 54% smoking), at point of sale (44% alcohol; 65% smoking) and on days leading up to the weekend (57% alcohol; 57% smoking). Exposures were also likely in the presence of family (69% alcohol; 56% smoking). Overall, results of this small pilot provide preliminary evidence that EMA is a useful tool for tracking and characterizing middle and high school students’ real-world exposures to alcohol and smoking-related media. Future studies may suggest mechanisms by which media exposures lead to youth uptake of drinking and smoking behaviors. PMID:23772763

Reducing youth exposure to alcohol ads: targeting public transit.

PubMed

Simon, Michele

2008-07-01

Underage drinking is a major public health problem. Youth drink more heavily than adults and are more vulnerable to the adverse effects of alcohol. Previous research has demonstrated the connection between alcohol advertising and underage drinking. Restricting outdoor advertising in general and transit ads in particular, represents an important opportunity to reduce youth exposure. To address this problem, the Marin Institute, an alcohol industry watchdog group in Northern California, conducted a survey of alcohol ads on San Francisco bus shelters. The survey received sufficient media attention to lead the billboard company, CBS Outdoor, into taking down the ads. Marin Institute also surveyed the 25 largest transit agencies; results showed that 75 percent of responding agencies currently have policies that ban alcohol advertising. However, as the experience in San Francisco demonstrated, having a policy on paper does not necessarily mean it is being followed. Communities must be diligent in holding accountable government officials, the alcohol industry, and the media companies through which advertising occurs.

Reducing Youth Exposure to Alcohol Ads: Targeting Public Transit

PubMed Central

2008-01-01

Underage drinking is a major public health problem. Youth drink more heavily than adults and are more vulnerable to the adverse effects of alcohol. Previous research has demonstrated the connection between alcohol advertising and underage drinking. Restricting outdoor advertising in general and transit ads in particular, represents an important opportunity to reduce youth exposure. To address this problem, the Marin Institute, an alcohol industry watchdog group in Northern California, conducted a survey of alcohol ads on San Francisco bus shelters. The survey received sufficient media attention to lead the billboard company, CBS Outdoor, into taking down the ads. Marin Institute also surveyed the 25 largest transit agencies; results showed that 75 percent of responding agencies currently have policies that ban alcohol advertising. However, as the experience in San Francisco demonstrated, having a policy on paper does not necessarily mean it is being followed. Communities must be diligent in holding accountable government officials, the alcohol industry, and the media companies through which advertising occurs. PMID:18389374

Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood.

PubMed

Kyzar, Evan J; Zhang, Huaibo; Sakharkar, Amul J; Pandey, Subhash C

2017-09-01

Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long-lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1 + 8a (a neuron-specific splice variant) in specific amygdaloid structures compared with AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2 g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1 + 8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the brain-derived neurotrophic factor exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety. © Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Alcohol- and light-induced electro-oculographic responses in age-related macular degeneration & central serous chorioretinopathy. alcohol- and light-induced EOG responses in ARMD & CSC.

PubMed

Wu, Kathy H C; Marmor, Michael F

2005-01-01

The non-photic electro-oculographic (EOG) response induced by alcohol has been proposed as an indicator of retinal pigment epithelial (RPE) integrity, and reported to be abnormal in age-related macular degeneration (ARMD). To evaluate this proposal, we have measured the alcohol-EOG as well as the ISCEV-standard EOG in patients with ARMD (n=11 patients, 4 eyes with drusen, 8 eyes with 'dry' and 7 eyes with 'wet' lesions) and central serous chorioretinopathy (CSC, n=11 patients, 7 eyes with active and 6 eyes with inactive lesions), compared with 29 normal controls. We recorded the alcohol-induced EOG response after a single oral administration of ethanol at 160 mg/kg, followed by an ISCEV-standard EOG. Blood alcohol levels were monitored with a breath analyzer. We found that neither the alcohol-EOG nor the light-induced EOG response showed any difference between either ARMD or CSC patients and normal controls. Nor was there difference among eyes of different ARMD or CSC subgroups. In addition, blood alcohol concentrations near the time of the alcohol-EOG peak showed no obvious relationship with peak/baseline ratios. These data suggest that neither the alcohol- nor the light-induced EOG is a sensitive indicator of these diseases.

Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.

PubMed

Ditzel, Eric J; Li, Hui; Foy, Caroline E; Perrera, Alec B; Parker, Patricia; Renquist, Benjamin J; Cherrington, Nathan J; Camenisch, Todd D

2016-07-01

Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease. © 2016 Wiley Periodicals, Inc.

The effect of intimate exposure to alcohol abuse on the acquisition of knowledge about drinking.

PubMed

Rainer, J P

1994-01-01

This study explored how an alcohol education program might be structured to effectively educate college students about the consequences of alcohol use. The primary hypothesis tested stated that individuals would vary significantly in the amount of knowledge learned from a structured alcohol education workshop, based on the degree of familial or social exposure s/he has had to alcohol abuse. Social learning variables of locus of control, dogmatism, and expectancy for risk were tested for interaction with degree of exposure, to determine their influence on learning. A pretest-posttest control group was employed with a sample of 66 undergraduate college students. A four hour alcohol education program was administered to teach cognitive information and fact about alcohol, with a goal of facilitating responsible use/nonuse of alcohol. The Student Drinking Questionnaire measured acquisition of knowledge. The Adult Nowicki-Strickland Internal/External Scale measured locus of control, and Schultze's Short Dogmatism Scale measured dogmatism. The researcher developed an instrument for expectancy for risk. Multiple regression analyses yielded prediction equations for the variables under study. For the sample group, results demonstrated that a significant portion of the variance in the residualized posttest scores was accounted for by level of exposure and dogmatism. When the sample was blocked according to intimate or social exposure, dogmatism was the only construct entering the regression equation at a significant level for the intimate exposure group. None of the constructs were able to predict any of the residualized posttest scores for the social exposure group. It was concluded that: (1) Students in the sample learned differentially based on the degree of intimate exposure of alcohol; (2) Dogmatism is a moderating variable with acquisition of knowledge for those intimately exposed to alcohol abuse, but locus of control and expectancy for risk are not; and (3) Further

The association of alcohol-induced blackouts and grayouts to blood alcohol concentrations.

PubMed

Perry, Paul J; Argo, Tami R; Barnett, Mitchell J; Liesveld, Jill L; Liskow, Barry; Hernan, Jillian M; Trnka, Michael G; Brabson, Mary A

2006-07-01

The primary aim of this study was to investigate the association between measured blood alcohol concentration (BAC) and the presence and degree of amnesia (no amnesia, grayout, or blackout) in actively drinking subjects. A secondary aim was to determine potential factors other than BAC that contribute to the alcohol-induced memory loss. An interview questionnaire was administered to subjects regarding a recent alcohol associated arrest with a documented BAC greater than 0.08 g/dL for either public intoxication, driving under the influence, or under age drinking was administered. Demographic variables collected included drinking history, family history of alcoholism, presence of previous alcohol-related memory loss during a drinking episode, and drinking behavior during the episode. Memory of the drinking episode was evaluated to determine if either an alcohol-induced grayout (partial anterograde amnesia) or blackout (complete anterograde amnesia) occurred. Differences in (1) mean total number of drinks ingested before arrest, (2) gulping of drinks, and (3) BAC at arrest were found for those having blackouts compared with no amnesia; while differences in drinking more than planned were found between the no amnesia and grayout groups. A strong linear relationship between BAC and predicted probability of memory loss, particularly for blackouts was obvious. This finding clinically concludes that subjects with BAC of 310 g/dL or greater have a 0.50 or greater probability of having an alcoholic blackout.

Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats.

PubMed

Sherrill, Luke K; Berthold, Claire; Koss, Wendy A; Juraska, Janice M; Gulley, Joshua M

2011-11-20

Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. Copyright © 2011 Elsevier B.V. All rights reserved.

Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats

PubMed Central

Sherrill, Luke K.; Berthold, Claire; Koss, Wendy A.; Juraska, Janice M.; Gulley, Joshua M.

2011-01-01

Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol s aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0 g/kg ethanol in a binge-like pattern during postnatal days (PD) 35–45. In adulthood (> PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5 g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. PMID:21767576

Neuropsychological deficits associated with heavy prenatal alcohol exposure are not exacerbated by ADHD.

PubMed

Glass, Leila; Ware, Ashley L; Crocker, Nicole; Deweese, Benjamin N; Coles, Claire D; Kable, Julie A; May, Philip A; Kalberg, Wendy O; Sowell, Elizabeth R; Jones, Kenneth Lyons; Riley, Edward P; Mattson, Sarah N

2013-11-01

Neuropsychological functioning of individuals with attention-deficit/hyperactivity disorder (ADHD) or heavy prenatal alcohol exposure has been well documented independently. This study examined the interaction between both factors on cognitive performance in children. As part of a multisite study, 344 children (8-16 y, M = 12.28, SD = 2.52) completed a comprehensive neuropsychological battery. Four subject groups were tested: children with histories of heavy prenatal alcohol exposure (AE) and ADHD (AE+, n = 90), alcohol-exposed without ADHD, (AE-, n = 38), nonexposed with ADHD (ADHD, n = 80), and nonexposed without ADHD (CON, n = 136). Separate 2(AE) × 2(ADHD) MANCOVAs revealed significant main and interactive effects of ADHD and AE on overall WISC-IV, D-KEFS, and CANTAB performance. Individual ANOVAs revealed significant interactions on 2 WISC-IV indices [Verbal Comprehension (VCI), Perceptual Reasoning (PRI)], and four D-KEFS and CANTAB subtests [Design Fluency, Verbal Fluency, Trail Making, Spatial Working Memory]. Follow-up analyses demonstrated no difference between AE+ and AE- groups on these measures. The combined AE+/- group demonstrated more severe impairment than the ADHD group on VCI and PRI, but there were no other differences between clinical groups. These results support a combined AE+/- group for neuropsychological research and indicate that, in some cases, the neuropsychological effects seen in ADHD are altered by prenatal alcohol exposure. The effects of alcohol exposure on verbal comprehension and perceptual reasoning were greater than those related to having ADHD without alcohol exposure, although both conditions independently resulted in cognitive impairment compared to controls. Clinically, these findings demonstrate task-dependent patterns of impairment across clinical disorders. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Neonatal alcohol exposure disrupts hippocampal neurogenesis and contextual fear conditioning in adult rats

PubMed Central

Hamilton, G.F.; Murawski, N.J.; St. Cyr, S.A.; Jablonski, S.A.; Schiffino, F.L.; Stanton, M.E.; Klintsova, A.Y.

2011-01-01

Developmental alcohol exposure can permanently alter brain structures and produce functional impairments in many aspects of behavior, including learning and memory. This study evaluates the effect of neonatal alcohol exposure on adult neurogenesis in the dentate gyrus of the hippocampus and the implications of such exposure for hippocampus-dependent contextual fear conditioning. Alcohol-exposed rats (AE) received 5.25 g/kg/day of alcohol on postnatal days (PD) 4-9 (third trimester in humans), in a binge-like manner. Two control groups were included: sham-intubated (SI) and suckle-control (SC). Animals were housed in social cages (3/cage) after weaning. On PD80, animals were injected with 200 mg/kg BrdU. Half of the animals were sacrificed two hours later. The remainder were sacrificed on PD114 to evaluate cell survival; separate AE, SI, and SC rats not injected with BrdU were tested for the context preexposure facilitation effect (CPFE; ∼PD117). There was no difference in the number of BrdU+ cells in AE, SI and SC groups on PD80. On PD114, cell survival was significantly decreased in AE rats, demonstrating that developmental alcohol exposure damages new cells' ability to incorporate into the network and survive. Behaviorally tested SC and SI groups preexposed to the training context 24h prior to receiving a 1.5mA 2s footshock froze significantly more during the context test than their counterparts preexposed to an alternate context. AE rats failed to show the CPFE. The current study shows the detrimental, long-lasting effects of developmental alcohol exposure on hippocampal adult neurogenesis and contextual fear conditioning. PMID:21816390

Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve male offspring.

PubMed

Asimes, AnnaDorothea; Torcaso, Audrey; Pinceti, Elena; Kim, Chun K; Zeleznik-Le, Nancy J; Pak, Toni R

2017-05-01

Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

PubMed Central

Sawant, Onkar B.; Ramadoss, Jayanth; Hankins, Gary D.; Wu, Guoyao

2014-01-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy. PMID:24810329

Cellular and molecular mechanisms of alcohol-induced osteopenia.

PubMed

Luo, Zhenhua; Liu, Yao; Liu, Yitong; Chen, Hui; Shi, Songtao; Liu, Yi

2017-12-01

Alcoholic beverages are widely consumed, resulting in a staggering economic cost in different social and cultural settings. Types of alcohol consumption vary from light occasional to heavy, binge drinking, and chronic alcohol abuse at all ages. In general, heavy alcohol consumption is widely recognized as a major epidemiological risk factor for chronic diseases and is detrimental to many organs and tissues, including bones. Indeed, recent findings demonstrate that alcohol has a dose-dependent toxic effect in promoting imbalanced bone remodeling. This imbalance eventually results in osteopenia, an established risk factor for osteoporosis. Decreased bone mass and strength are major hallmarks of osteopenia, which is predominantly attributed not only to inhibition of bone synthesis but also to increased bone resorption through direct and indirect pathways. In this review, we present knowledge to elucidate the epidemiology, potential pathogenesis, and major molecular mechanisms and cellular effects that underlie alcoholism-induced bone loss in osteopenia. Novel therapeutic targets for correcting alcohol-induced osteopenia are also reviewed, such as modulation of proinflammatory cytokines and Wnt and mTOR signaling and the application of new drugs.

Resveratrol protects the loss of connexin 43 induced by ethanol exposure in neonatal mouse cardiomyocytes.

PubMed

Tu, Su; Cao, Fu-Tao; Fan, Xiao-Chun; Yang, Cheng-Jian

2017-06-01

Excessive alcohol consumption provides risk to cardiomyopathy with unknown mechanisms. Resveratrol, a plant polyphenol, is widely reported for its cardiovascular benefits, while its effect on alcohol-induced impairments in cardiomyocytes largely remains unknown. Effects of resveratrol on the cardiomyocytes under ethanol insult were studied in vitro. Ethanol exposure in mouse neonatal cardiomyocytes increased cell death and induced a specific loss of tight junction protein, connexin 43. In spite of adverse effects at higher concentrations, resveratrol at 10 μM improved cell viability of cardiomyocytes in the presence of a deleterious dose of ethanol. Importantly, the co-treatment of resveratrol with ethanol exhibited the restoration of connexin 43 protein. Further assays showed that these effects were likely associated with the antioxidative actions of resveratrol, and correlated with the alleviation of MAP kinase activation in cultured cardiomyocytes in response to ethanol. Our data suggests a novel mechanism of cardiomyocyte cell loss under ethanol exposure and provides new evidence of protective effects of resveratrol in the cardiomyocytes.

Youth exposure to alcohol advertising on radio--United States, June-August 2004.

PubMed

2006-09-01

In the United States, more underage youth drink alcohol than smoke tobacco or use illicit drugs. Excessive alcohol consumption leads to many adverse health and social consequences and results in approximately 4,500 deaths among underage youth each year. Recent studies have emphasized the contribution of alcohol marketing to underage drinking and have demonstrated that a substantial proportion of alcohol advertising appears in media for which the audience composition is youth-oriented (i.e., composed disproportionately of persons aged 12-20 years). To determine the proportion of radio advertisements that occurred on radio programs with audiences composed disproportionately of underage youth and the proportion of total youth exposure to alcohol advertising that occurs as a result of such advertising, researchers at the Center on Alcohol Marketing and Youth (Health Policy Institute, Georgetown University, District of Columbia) evaluated the placement of individual radio advertisements for the most advertised U.S. alcohol brands and the composition of audiences in the largest 104 markets in the United States. This report summarizes the results of that study, which indicate that alcohol advertising is common on radio programs which have disproportionately large youth audiences and that this advertising accounts for a substantial proportion of all alcohol radio advertising heard by underage youth. These results further indicate that 1) the current voluntary standards limiting alcohol marketing to youth should be enforced and ultimately strengthened, and 2) ongoing monitoring of youth exposure to alcohol advertising should continue.

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement

PubMed Central

Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.

2014-01-01

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2–24 hours post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16–24 hpf) produced retinal defects like those seen with ethanol exposure between 2–24 hpf. Significantly, during an ethanol-sensitive time window (16–24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. PMID:25541501

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.

PubMed

Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A

2015-03-01

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. Copyright © 2015 Elsevier Inc. All rights reserved.

Alcohol Advertising Exposure Among Middle School–Age Youth: An Assessment Across All Media and Venues

PubMed Central

Collins, Rebecca L.; Martino, Steven C.; Kovalchik, Stephanie A.; Becker, Kirsten M.; Shadel, William G.; D’Amico, Elizabeth J.

2016-01-01

Objective: The purpose of this study was to quantify middle school youth’s exposure to alcohol advertisements across media and venues, determine venues of greatest exposure, and identify characteristics of youth who are most exposed. Method: Over a 10-month period in 2013, 589 Los Angeles–area youth ages 11–14 from diverse racial/ethnic backgrounds completed a short paper-and-pencil survey assessing background characteristics and then participated in a 14-day ecological momentary assessment, logging all exposures to alcohol advertisements on handheld computers as they occurred. Results: African American and Hispanic youth were exposed to an average of 4.1 and 3.4 advertisements per day, respectively, nearly two times as many as non-Hispanic White youth, who were exposed to 2.0 advertisements per day. Girls were exposed to 30% more advertisements than boys. Most exposures were to outdoor advertisements, with television advertisements a close second. Conclusions: Exposure to alcohol advertising is frequent among middle school–age youth and may put them at risk for earlier or more frequent underage drinking. Greater restrictions on alcohol advertising outdoors and on television should be considered by regulators and by the alcohol industry and should focus particularly on reducing exposure among minority youth. PMID:27172570

Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models of PAE.

PubMed

Petrelli, Berardino; Weinberg, Joanne; Hicks, Geoffrey G

2018-04-01

The potential impact of prenatal alcohol exposure (PAE) varies considerably among exposed individuals, with some displaying serious alcohol-related effects and many others showing few or no overt signs of fetal alcohol spectrum disorder (FASD). In animal models, variables such as nutrition, genetic background, health, other drugs, and stress, as well as dosage, duration, and gestational timing of exposure to alcohol can all be controlled in a way that is not possible in a clinical situation. In this review we examine mouse models of PAE and focus on those with demonstrated craniofacial malformations, abnormal brain development, or behavioral phenotypes that may be considered FASD-like outcomes. Analysis of these data should provide a valuable tool for researchers wishing to choose the PAE model best suited to their research questions or to investigate established PAE models for FASD comorbidities. It should also allow recognition of patterns linking gestational timing, dosage, and duration of PAE, such as recognizing that binge alcohol exposure(s) during early gestation can lead to severe FASD outcomes. Identified patterns could be particularly insightful and lead to a better understanding of the molecular mechanisms underlying FASD.

Sex differences in reinstatement of alcohol seeking in response to cues and yohimbine in rats with and without a history of adolescent corticosterone exposure.

PubMed

Bertholomey, M L; Nagarajan, V; Torregrossa, Mary M

2016-06-01

Women represent a vulnerable and growing population with respect to alcohol abuse. Elevated glucocorticoid exposure in adolescence increases addiction risk and stress sensitivity in adulthood. However, little is known about sex differences in ethanol craving-like behavior. This study characterized sex differences in ethanol-motivated behavior following ethanol-paired cues and/or acute stimulation of the HPA axis in male and female rats with or without exposure to chronically elevated glucocorticoids in adolescence. Adolescent corticosterone-treated (Experiment 1) or naïve (Experiment 2) male and female rats were trained as adults to self-administer ethanol paired with a cue, and tested for the effects of this cue, alone or in combination with yohimbine, on the reinstatement of ethanol seeking. Females showed elevated ethanol self-administration and seeking compared to males. In Experiment 1, corticosterone exposure in adolescence augmented cue-induced reinstatement of ethanol seeking in females only, and females were more sensitive to yohimbine in promoting reinstatement. Experiment 2 replicated these findings and showed that exposure to both yohimbine and alcohol-related cues enhanced the reinstatement of alcohol seeking, producing additive effects in females. Corticosterone levels were higher in females and in yohimbine-treated rats, and corticosterone and estradiol correlated with responding during reinstatement. Chronic manipulations in adolescence and acute manipulations in adulthood of the HPA axis increase cue-induced reinstatement of ethanol seeking to a greater degree in females than in males. Elucidating the mechanisms that underlie these effects may lead to the development of sex-specific interventions aimed at mitigating alcohol relapse risk in females.

Alcohol-Induced Impairment of Balance is Antagonized by Energy Drinks.

PubMed

Marczinski, Cecile A; Fillmore, Mark T; Stamates, Amy L; Maloney, Sarah F

2018-01-01

The acute administration of alcohol reliably impairs balance and motor coordination. While it is common for consumers to ingest alcohol with other stimulant drugs (e.g., caffeine, nicotine), little is known whether prototypical alcohol-induced balance impairments are altered by stimulant drugs. The purpose of this study was to examine whether the coadministration of a high-caffeine energy drink with alcohol can antagonize expected alcohol-induced increases in body sway. Sixteen social drinkers (of equal gender) participated in 4 separate double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. Following dose administration, participants completed automated assessments of balance stability (both eyes open and eyes closed) measured using the Biosway Portable Balance System. Participants completed several subjective measures including self-reported ratings of sedation, stimulation, fatigue, and impairment. Blood pressure and pulse rate were recorded repeatedly. The acute administration of alcohol increased body sway, and the coadministration of energy drinks antagonized this impairment. When participants closed their eyes, alcohol-induced body sway was similar whether or not energy drinks were ingested. While alcohol administration increased ratings of sedation and fatigue, energy drink administration increased ratings of stimulation and reduced ratings of fatigue. Modest increases in systolic and diastolic blood pressure following energy drink administration were also observed. Visual assessment of balance impairment is frequently used to indicate that an individual has consumed too much alcohol (e.g., as part of police-standardized field sobriety testing or by a bartender assessing when someone should no longer be served more alcohol). The current findings suggest that energy drinks can antagonize alcohol-induced increases in body sway, indicating that future work is needed to determine whether this

Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive α1 GABAA receptors

PubMed Central

Werner, David F.; Swihart, Andrew R.; Ferguson, Carolyn; Lariviere, William R.; Harrison, Neil L.; Homanics, Gregg E.

2009-01-01

Background Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, γ-aminobutyric acid type A receptors (GABAA-Rs) have been extensively implicated in ethanol action. The α1 GABAA-R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that α1-GABAA-Rs mediate in part these effects of ethanol. Methods Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin mice that have ethanol-insensitive α1 GABAA-Rs and wildtype controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex assays. Chronic tolerance was assessed on the loss of righting reflex, fixed speed rotarod, hypothermia, and radiant tail flick assays following ten consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess α1 protein levels. Results Compared to controls, knockin mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between wildtype and knockin mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in α1 protein levels, but knockins did not. Conclusions We conclude that α1-GABAA-Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on α1-containing GABAA-Rs. PMID:19032579

Race, Ethnicity, and Exposure to Alcohol Outlets

PubMed Central

Morrison, Christopher; Gruenewald, Paul J.; Ponicki, William R.

2016-01-01

Objective: Prior studies suggest that Black and Hispanic minority populations are exposed to greater concentrations of alcohol outlets, potentially contributing to health disparities between these populations and the White majority. We tested the alternative hypothesis that urban economic systems cause outlets to concentrate in low-income areas and, controlling for these effects, lower demand among minority populations leads to fewer outlets. Method: Market potential for alcohol sales, a surrogate for demand, was estimated from survey and census data across census block groups for 50 California cities. Hierarchical Bayesian conditional autoregressive Poisson models then estimated relationships between observed geographic distributions of outlets and the market potential for alcohol, income, population size, and racial and ethnic composition. Results: Market potentials were significantly smaller among lower income Black, Hispanic, and Asian populations. Block groups with greater market potential and lower income had greater concentrations of outlets. When we controlled for these effects, the racial and ethnic group composition of block groups was mostly unrelated to outlet concentrations. Conclusions: Health disparities related to exposure to alcohol outlets are primarily driven by distributions of income and population density across neighborhoods. PMID:26751356

Watching and drinking: Expectancies, prototypes, and peer affiliations mediate the effect of exposure to alcohol use in movies on adolescent drinking

PubMed Central

Dal Cin, Sonya; Worth, Keilah A.; Gerrard, Meg; Gibbons, Frederick X.; Stoolmiller, Mike; Wills, Thomas A.; Sargent, James D.

2009-01-01

Objective To investigate the psychological processes that underlie the relation between exposure to alcohol use in media with adolescent alcohol use. Design Structural equation modeling analysis of data from four waves of a longitudinal, nationally-representative, random-digit dial telephone survey of adolescents in the United States. Main Outcome Measures Adolescent alcohol consumption and willingness to use alcohol. Tested mediators were alcohol-related norms, prototypes, expectancies, and friends' use. Results Alcohol prototypes, expectancies, willingness, and friends' use of alcohol (but not perceived prevalence of alcohol use among peers) were significant mediators of the relation between movie alcohol exposure and alcohol consumption, even after controlling for demographic, child, and family factors associated with both movie exposure and alcohol consumption. Conclusion Established psychological and interpersonal predictors of alcohol use mediate the effects of exposure to alcohol use in movies on adolescent alcohol consumption. The findings suggest that exposure movie portrayals may operate through similar processes as other social influences, highlighting the importance of considering these exposures in research on adolescent risk behavior. PMID:19594272

Identification of Noninvasive Biomarkers for Alcohol-Induced Liver Disease Using Urinary Metabolomics and the Ppara-null Mouse

PubMed Central

Manna, Soumen K.; Patterson, Andrew D.; Yang, Qian; Krausz, Kristopher W.; Li, Henghong; Idle, Jeffrey R.; Fornace, Albert J.; Gonzalez, Frank J.

2010-01-01

Alcohol-induced liver disease (ALD) is a leading cause of non-accident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively non-specific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study the metabolic changes associated with alcohol-induced liver disease were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-β-D-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model. PMID:20540569

Exploring associations between prenatal solvent exposures and teenage drug and alcohol use: a retrospective cohort study.

PubMed

Gallagher, Lisa G; Webster, Thomas F; Aschengrau, Ann

2017-03-11

Investigating the effects of prenatal and childhood exposures on behavioral health outcomes in adolescence is challenging given the lengthy period between the exposure and outcomes. We conducted a retrospective cohort study in Cape Cod, Massachusetts to evaluate the impact of prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water on the occurrence of risk-taking behaviors as a teenager. An increased occurrence of risk-taking behaviors, particularly illicit drug use, was observed in those highly exposed to PCE. We hypothesized that there may be other sources of prenatal solvent exposure such as maternal consumption of alcoholic beverages during pregnancy which might modify the previously observed associations between PCE and risk-taking behaviors and so we conducted an exploratory analysis using available cohort data. The current report presents the results of these analyses and describes the difficulties in conducting research on long-term behavioral effects of early life exposures. The exploratory analysis compared a referent group of subjects with no early life exposure to PCE or alcohol (n = 242) to subjects with only alcohol exposure (n = 201), subjects with only PCE exposure (n = 361), and subjects with exposure to both PCE and alcohol (n = 302). Surveys completed by the subject's mother included questions on prenatal alcoholic beverage consumption and available confounding variables such as cigarette smoking and marijuana use. Surveys completed by the subjects included questions on risk-taking behaviors such as alcoholic beverage consumption and illicit drug use as a teenager and available confounding variables. PCE exposure was modeled using a leaching and transport algorithm embedded in water distribution system modeling software that estimated the amount of PCE delivered to a subject's residence during gestation and early childhood. Subjects with early life exposure to both PCE and alcohol had an

Atypical Cortical Gyrification in Adolescents with Histories of Heavy Prenatal Alcohol Exposure

PubMed Central

Infante, M. Alejandra; Moore, Eileen M.; Bischoff-Grethe, Amanda; Migliorini, Robyn; Mattson, Sarah N.; Riley, Edward P.

2015-01-01

Prenatal alcohol exposure can adversely affect brain development, although little is known about the effects of prenatal alcohol exposure on gyrification. Gyrification reflects cortical folding complexity and is a process by which the surface of the brain creates sulci and gyri. Prior studies have shown that prenatal alcohol exposure is associated with reduced gyrification in childhood, but no studies have examined adolescents. Subjects (12–16y) comprised two age-equivalent groups: 30 adolescents with histories of heavy prenatal alcohol exposure (AE) and 19 non-exposed controls (CON). A T1-weighted image was obtained for all participants. Local gyrification index (LGI) was estimated using FreeSurfer. General linear models were used to determine between group differences in LGI controlling for age and sex. Age-by-group interactions were also investigated while controlling for sex. The AE group displayed reduced LGI relative to CON in the bilateral superior parietal region, right postcentral region, and left precentral and lateral occipital regions (ps < .001). Significant age-by-group interactions were observed in the right precentral and lateral occipital regions, and in the left pars opercularis and inferior parietal regions (ps < .01). The AE group showed age-related reductions in gyrification in all regions whereas the CON group showed increased gyrification with age in the lateral occipital region only. While cross-sectional, the age-related reduction in gyrification observed in the AE group suggests alterations in cortical development throughout adolescence and provides further insight into the pathophysiology and brain maturation of adolescents prenatally exposed to alcohol. PMID:26275919

[Brazilian teenagers and beer advertising: relationship between exposure, positive response, and alcohol consumption].

PubMed

Vendrame, Alan; Pinsky, Ilana; Faria, Roberta; Silva, Rebeca

2009-02-01

Brazilian teenagers report problematic patterns of alcohol consumption. Alcohol advertising strategies are one of the main factors influencing adolescents' alcohol consumption. The aim of this study was to evaluate the relationship between positive responses to TV beer commercials, exposure, and alcohol consumption. Thirty-two recent TV commercials were shown to 133 high school students from public schools in São Bernardo do Campo, São Paulo State, Brazil. The subjects recorded how well they liked the ads and how often they had already watched each commercial. The teenagers also reported their alcohol consumption rates. The ten commercials analyzed in this article were the five most popular and the five least popular. The analysis showed that subjects had already seen the five most popular ads, but not the five least popular. In addition, the five most popular ads received higher scores from teenagers that reported having consumed beer during the previous month. The study found a positive relationship between enjoying beer advertising and exposure to beer ads, as well as between alcohol consumption and positive responses to alcohol commercials.

Impulsive Choice, Alcohol Consumption, and Pre-Exposure to Delayed Rewards: II. Potential Mechanisms

PubMed Central

Stein, Jeffrey S.; Renda, C. Renee; Hinnenkamp, Jay E.; Madden, Gregory J.

2014-01-01

In a prior study (Stein et al., 2013), we reported that rats pre-exposed to delayed rewards made fewer impulsive choices, but consumed more alcohol (12% wt/vol), than rats pre-exposed to immediate rewards. To understand the mechanisms that produced these findings, we again pre-exposed rats to either delayed (17.5 s; n = 32) or immediate (n = 30) rewards. In post-tests, delay-exposed rats made significantly fewer impulsive choices at both 15- and 30-s delays to a larger, later food reward than the immediacy-exposed comparison group. Behavior in an open-field test provided little evidence of differential stress exposure between groups. Further, consumption of either 12% alcohol or isocaloric sucrose in subsequent tests did not differ between groups. Because Stein et al. introduced alcohol concentration gradually (3–12%), we speculate that their group differences in 12% alcohol consumption were not determined by alcohol’s pharmacological effects, but by another variable (e.g., taste) that was preserved as an artifact from lower concentrations. We conclude that pre-exposure to delayed rewards generalizes beyond the pre-exposure delay; however, this same experimental variable does not robustly influence alcohol consumption. PMID:25418607

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol.

PubMed

Sawant, Onkar B; Ramadoss, Jayanth; Hankins, Gary D; Wu, Guoyao; Washburn, Shannon E

2014-08-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75-2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid-base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid-base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.

Youth alcohol brand consumption and exposure to brand advertising in magazines.

PubMed

Ross, Craig S; Ostroff, Joshua; Siegel, Michael B; DeJong, William; Naimi, Timothy S; Jernigan, David H

2014-07-01

Recently published research has identified the alcohol brands most frequently consumed by underage youth. The present study examines alcohol magazine advertising in 2011 to report age- and sex-specific exposure to advertisements for these brands in contrast with other magazine advertising brands less popular with youth. We licensed magazine advertising occurrence data from Nielsen and magazine audience data from the research company GfK MRI (Growth from Knowledge, Mediamark Research & Intelligence) for national full-run editions for 2011. We contrasted per capita advertising exposure, considering different age- and sex-specific groups, for popular youth brands versus all other magazine brands. For each brand, we reported the age group receiving the highest level of per capita advertising exposure, as well as other age groups within 10% of that peak level. Underage males ages 18-20 were the most heavily exposed age group for 11 of the top 25 brands they consumed and were within 10% of the most heavily exposed group for another 6 brands. Underage females ages 18-20 were most heavily exposed for 16 of the top 25 brands they consumed and were within 10% of the most heavily exposed group for another 2 brands. In contrast, those ages 18-20 were the most heavily exposed group for fewer than 10% of the remaining 308 magazine advertising brands for either sex. These findings suggest a relationship between advertising exposure and youth alcohol brand consumption. Current alcohol industry self-regulatory codes may not be sufficiently protective of youth.

Youth Alcohol Brand Consumption and Exposure to Brand Advertising in Magazines

PubMed Central

Ross, Craig S; Ostroff, Joshua; Siegel, Michael B; DeJong, William; Naimi, Timothy S; Jernigan, David H

2014-01-01

Objective: Recently published research has identified the alcohol brands most frequently consumed by underage youth. The present study examines alcohol magazine advertising in 2011 to report age- and sex-specific exposure to advertisements for these brands in contrast with other magazine advertising brands less popular with youth. Method: We licensed magazine advertising occurrence data from Nielsen and magazine audience data from the research company GfK MRI (Growth from Knowledge, Mediamark Research & Intelligence) for national full-run editions for 2011. We contrasted per capita advertising exposure, considering different age- and sex-specific groups, for popular youth brands versus all other magazine brands. For each brand, we reported the age group receiving the highest level of per capita advertising exposure, as well as other age groups within 10% of that peak level. Results: Underage males ages 18–20 were the most heavily exposed age group for 11 of the top 25 brands they consumed and were within 10% of the most heavily exposed group for another 6 brands. Underage females ages 18–20 were most heavily exposed for 16 of the top 25 brands they consumed and were within 10% of the most heavily exposed group for another 2 brands. In contrast, those ages 18–20 were the most heavily exposed group for fewer than 10% of the remaining 308 magazine advertising brands for either sex. Conclusions: These findings suggest a relationship between advertising exposure and youth alcohol brand consumption. Current alcohol industry self-regulatory codes may not be sufficiently protective of youth. PMID:24988260

Youth exposure to alcohol advertising on television in the UK, the Netherlands and Germany.

PubMed

Patil, Sunil; Winpenny, Eleanor M; Elliott, Marc N; Rohr, Charlene; Nolte, Ellen

2014-08-01

Exposure of young people to alcohol advertising is a risk factor for underage drinking. This study assessed youth exposure to television alcohol advertising in the UK, the Netherlands and Germany, from December 2010 to May 2011. A negative binomial regression model predicted number of alcohol advertisements from the proportion of the television viewership in each age group. This allowed comparison of alcohol advertisement incidence for each youth age category relative to an adult reference category. In the UK, those aged 10-15 years were significantly more exposed to alcohol advertisements per viewing hour than adults aged ≥ 25 years [incidence rate ratio (IRR) = 1.11; 95% confidence interval (95% CI): 1.06, 1.18; P < 0.01]; in the Netherlands, those aged 13-19 years were more exposed per viewing hour than adults aged ≥ 20 years (IRR = 1.29; 95% CI: 1.19, 1.39; P < 0.01). Conversely, in Germany, those aged 10-15 years were less exposed to alcohol advertisements than adults aged ≥ 25 years (IRR = 0.79; 95% CI: 0.73, 0.85; P < 0.01). In each country, young children (aged 4-9 years in the UK and Germany, 6-12 years in the Netherlands) were less exposed than adults. Adolescents in the UK and the Netherlands, but not Germany, had higher exposure to television alcohol advertising relative to adults than would be expected from their television viewing. Further work across a wider range of countries is needed to understand the relationship between national policies and youth exposure to alcohol advertising on television. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Alcohol and Apoptosis: Friends or Foes?

PubMed

Rodriguez, Ana; Chawla, Karan; Umoh, Nsini A; Cousins, Valerie M; Ketegou, Assama; Reddy, Madhumati G; AlRubaiee, Mustafa; Haddad, Georges E; Burke, Mark W

2015-11-19

Alcohol abuse causes 79,000 deaths stemming from severe organ damage in the United States every year. Clinical manifestations of long-term alcohol abuse on the cardiac muscle include defective contractility with the development of dilated cardiomyopathy and low-output heart failure; which has poor prognosis with less than 25% survival for more than three years. In contrast, low alcohol consumption has been associated with reduced risk of cardiovascular disease, however the mechanism of this phenomenon remains elusive. The aim of this study was to determine the significance of apoptosis as a mediating factor in cardiac function following chronic high alcohol versus low alcohol exposure. Adult rats were provided 5 mM (low alcohol), 100 mM (high alcohol) or pair-fed non-alcohol controls for 4-5 months. The hearts were dissected, sectioned and stained with cresyl violet or immunohistochemically for caspase-3, a putative marker for apoptosis. Cardiomyocytes were isolated to determine the effects of alcohol exposure on cell contraction and relaxation. High alcohol animals displayed a marked thinning of the left ventricular wall combined with elevated caspase-3 activity and decreased contractility. In contrast, low alcohol was associated with increased contractility and decreased apoptosis suggesting an overall protective mechanism induced by low levels of alcohol exposure.

Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome.

PubMed

Hoyt, Laura R; Randall, Matthew J; Ather, Jennifer L; DePuccio, Daniel P; Landry, Christopher C; Qian, Xi; Janssen-Heininger, Yvonne M; van der Vliet, Albert; Dixon, Anne E; Amiel, Eyal; Poynter, Matthew E

2017-08-01

Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation. Here we show that long-term ethanol exposure of human peripheral blood mononuclear cells and a mouse macrophage cell line (J774) amplifies IL-1β secretion following stimulation with NLRP3 agonists, but not with AIM2 or NLRP1b agonists. The augmented NRLP3 activation was mediated by increases in iNOS expression and NO production, in conjunction with increases in mitochondrial membrane depolarization, oxygen consumption rate, and ROS generation in J774 cells chronically exposed to ethanol (CE cells), effects that could be inhibited by the iNOS inhibitor SEITU, the NO scavenger carboxy-PTIO, and the mitochondrial ROS scavenger MitoQ. Chronic ethanol exposure did not alter K + efflux or Zn 2+ homeostasis in CE cells, although it did result in a lower intracellular concentration of NAD + . Prolonged administration of acetaldehyde, the product of alcohol dehydrogenase (ADH) mediated metabolism of ethanol, mimicked chronic ethanol exposure, whereas ADH inhibition prevented ethanol-induced IL-1β hypersecretion. Together, these results indicate that increases in iNOS and mitochondrial ROS production are critical for chronic ethanol-induced IL-1β hypersecretion, and that protracted exposure to the products of ethanol metabolism are probable mediators of NLRP3 inflammasome hyperactivation. Copyright © 2017. Published by Elsevier

Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues.

PubMed

George, M S; Anton, R F; Bloomer, C; Teneback, C; Drobes, D J; Lorberbaum, J P; Nahas, Z; Vincent, D J

2001-04-01

Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique. Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

Molecular mechanisms of synaptic remodeling in alcoholism

PubMed Central

Kyzar, Evan J.; Pandey, Subhash C.

2015-01-01

Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the “dark side” of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. PMID:25623036

Molecular mechanisms of synaptic remodeling in alcoholism.

PubMed

Kyzar, Evan J; Pandey, Subhash C

2015-08-05

Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. Published by Elsevier Ireland Ltd.

A Decision Tree to Identify Children Affected by Prenatal Alcohol Exposure

PubMed Central

Goh, Patrick K.; Doyle, Lauren R.; Glass, Leila; Jones, Kenneth L.; Riley, Edward P.; Coles, Claire D.; Hoyme, H. Eugene; Kable, Julie A.; May, Philip A.; Kalberg, Wendy O.; Elizabeth, R. Sowell; Wozniak, Jeffrey R.; Mattson, Sarah N.

2017-01-01

Objective To develop and validate a hierarchical decision tree model, combining neurobehavioral and physical measures, for identification of children affected by prenatal alcohol exposure even when facial dysmorphology is not present. Study design Data were collected as part of a multisite study across the United States. The model was developed after evaluating over 1000 neurobehavioral and dysmorphology variables collected from 434 children (8–16y) with prenatal alcohol exposure, with and without fetal alcohol syndrome (FAS), and non-exposed controls, with and without other clinically-relevant behavioral or cognitive concerns. The model was subsequently validated in an independent sample of 454 children in two age ranges (5–7y or 10–16y). In all analyses, the discriminatory ability of each model step was tested with logistic regression. Classification accuracies and positive and negative predictive values were calculated. Results The model consisted of variables from 4 measures (2 parent questionnaires, an IQ score, and a physical examination). Overall accuracy rates for both the development and validation samples met or exceeded our goal of 80% overall accuracy. Conclusions The decision tree model distinguished children affected by prenatal alcohol exposure from non-exposed controls, including those with other behavioral concerns or conditions. Improving identification of this population will streamline access to clinical services, including multidisciplinary evaluation and treatment. PMID:27476634

Changes in the α4β2* nicotinic acetylcholine system during chronic controlled alcohol exposure in nonhuman primates.

PubMed

Hillmer, Ansel T; Tudorascu, Dana L; Wooten, Dustin W; Lao, Patrick J; Barnhart, Todd E; Ahlers, Elizabeth O; Resch, Leslie M; Larson, Julie A; Converse, Alexander K; Moore, Colleen F; Schneider, Mary L; Christian, Bradley T

2014-05-01

The precise nature of modifications to the nicotinic acetylcholine receptor (nAChR) system in response to chronic ethanol exposure is poorly understood. The present work used PET imaging to assay α4β2* nAChR binding levels of eight rhesus monkeys before and during controlled chronic ethanol intake. [(18)F]Nifene PET scans were conducted prior to alcohol exposure, and then again after at least 8 months controlled ethanol exposure, including 6 months at 1.5 g/kg/day following a dose escalation period. Receptor binding levels were quantified with binding potentials (BPND) using the cerebellum as a reference region. Alcohol self-administration was assessed as average daily alcohol intake during a 2 month free drinking period immediately following controlled alcohol. Significant decreases in α4β2* nAChR binding were observed in both frontal and insular cortex in response to chronic ethanol exposure. During chronic alcohol exposure, BPND in the lateral geniculate region correlated positively with the amount of alcohol consumed during free drinking. The observed decreases in nAChR availability following chronic alcohol consumption suggest alterations to this receptor system in response to repeated alcohol administration, making this an important target for further study in alcohol abuse and alcohol and nicotine codependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

An examination of sex differences in the effects of early-life opiate and alcohol exposure

PubMed Central

Terasaki, Laurne S.; Gomez, Julie; Schwarz, Jaclyn M.

2016-01-01

Early-life exposure to drugs and alcohol is one of the most preventable causes of developmental, behavioural and learning disorders in children. Thus a significant amount of basic, animal and human research has focused on understanding the behavioural consequences and the associated neural effects of exposure to drugs and alcohol during early brain development. Despite this, much of the previous research that has been done on this topic has used predominantly male subjects or rodents. While many of the findings from these male-specific studies may ultimately apply to females, the purpose of this review is to highlight the research that has also examined sex as a factor and found striking differences between the sexes in their response to early-life opiate and alcohol exposure. Finally, we will also provide a framework for scientists interested in examining sex as a factor in future experiments that specifically examine the consequences of early-life drug and alcohol exposure. PMID:26833841

Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

PubMed

Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

2016-10-01

As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Salt-Inducible Kinase 1 (SIK1) is Induced by Alcohol and Suppresses Microglia Inflammation via NF-κB Signaling.

PubMed

Zhang, Yu; Gao, Weida; Yang, Kongbin; Tao, Haiquan; Yang, Haicheng

2018-06-19

Alcohol consumption has been shown to cause neuroinflammation and increase a variety of immune-related signaling processes. Microglia are a crucial part of alcohol-induced neuroinflammation and undergo apoptosis. Even though the importance of these inflammatory processes in the effects of alcohol-related neurodegeneration have been established, the mechanism of alcohol-induced microglia apoptosis is unknown. In prior research, we discovered that alcohol increases expression of salt-inducible kinase 1 (SIK1) in rodent brain tissue. In this study, we sought to determine what role SIK1 expression plays in alcohol-induced neuroinflammation as well as whether and by what mechanism it regulates microglia apoptosis. Adult C57BL/6 mice were divided into four groups and for 3 weeks treated with either 0%, 5%, 10%, or 15% alcohol during 3 hour periods. The mice were sacrificed and their brains excised for analysis. Additionally, primary microglia were isolated from neonatal mice. SIK1 expression in alcohol-treated brain tissue and microglia was analyzed via RT-PCR and western blotting. TUNEL staining, caspase-3, and caspase-9 activity assays were performed to evaluate microglial apoptosis. Cell fluorescence staining and NF-κB luciferase activity assays were used to evaluate the effects of SIK1 expression on the NF-κB signaling pathway. SIK1 expression was increased in the brains of mice that consumed alcohol, and this effect was seen in mouse primary microglia. SIK1 knockdown in microglia increased alcohol-induced apoptosis in these cells. Furthermore, SIK1 reduced NF-κB signaling pathway factors, and SIK1 knockdown in microglia promoted alcohol-induced NF-κB activity. TUNEL staining, caspase-3, and caspase-9 activity assays consistently revealed that alcohol-induced microglial apoptosis was inhibited by depletion of p65. Finally, we determined that NF-κB signaling is required for alcohol-induced, SIK1-mediated apoptosis in microglia. This study establishes for the

Changes in the Relative Balance of Approach and Avoidance Inclinations to Use Alcohol Following Cue Exposure Vary in Low and High Risk Drinkers

PubMed Central

Hollett, Ross C.; Stritzke, Werner G. K.; Edgeworth, Phoebe; Weinborn, Michael

2017-01-01

According to the ambivalence model of craving, alcohol craving involves the dynamic interplay of separate approach and avoidance inclinations. Cue-elicited increases in approach inclinations are posited to be more likely to result in alcohol consumption and risky drinking behaviors only if unimpeded by restraint inclinations. Current study aims were (1) to test if changes in the net balance between approach and avoidance inclinations following alcohol cue exposure differentiate between low and high risk drinkers, and (2) if this balance is associated with alcohol consumption on a subsequent taste test. In two experiments (N = 60; N = 79), low and high risk social drinkers were exposed to alcohol cues, and pre- and post- approach and avoidance inclinations measured. An ad libitum alcohol consumption paradigm and a non-alcohol exposure condition were also included in Study 2. Cue-elicited craving was characterized by a predominant approach inclination only in the high risk drinkers. Conversely, approach inclinations were adaptively balanced by equally strong avoidance inclinations when cue-elicited craving was induced in low risk drinkers. For these low risk drinkers with the balanced craving profile, neither approach or avoidance inclinations predicted subsequent alcohol consumption levels during the taste test. Conversely, for high risk drinkers, where the approach inclination predominated, each inclination synergistically predicted subsequent drinking levels during the taste test. In conclusion, results support the importance of assessing both approach and avoidance inclinations, and their relative balance following alcohol cue exposure. Specifically, this more comprehensive assessment reveals changes in craving profiles that are not apparent from examining changes in approach inclinations alone, and it is this shift in the net balance that distinguishes high from low risk drinkers. PMID:28533759

Exposure to Terrorism and Israeli Youths’ Cigarette, Alcohol, and Cannabis Use

PubMed Central

Schiff, Miriam; Zweig, Hillah Haim; Benbenishty, Rami; Hasin, Deborah S.

2007-01-01

Objectives. We investigated the consequences of exposure to acts of terrorism among Israeli adolescents. We examined whether exposure to terrorism predicted adolescents’ use of cigarettes, alcohol (including binge drinking), and cannabis after we controlled for posttraumatic stress and depressive symptoms and background variables. Methods. Anonymous self-administered questionnaires were given to a random sample of 960 10th and 11th grade students (51.6% boys, 48.4% girls) in a large city in northern Israel. Results. Close physical exposure to acts of terrorism predicted higher levels of alcohol consumption (including binge drinking among drinkers) and cannabis use. These relationships remained even after we controlled for posttraumatic stress and depressive symptoms. Conclusions. In addition to posttraumatic stress symptoms, negative consequences of terrorism exposure among adolescents included substance abuse. The similarity between our findings among Israeli adolescents and previous findings among US adults suggests cross-cultural generalizability. Given the risks for later problems from early-onset substance abuse, the consequences of terrorism exposure among adolescents merit greater research and clinical attention. PMID:17761574

Socioeconomic determinants of exposure to alcohol outlets.

PubMed

Morrison, Christopher; Gruenewald, Paul J; Ponicki, William R

2015-05-01

Alcohol outlets tend to be located in lower income areas, exposing lower income populations to excess risks associated with alcohol sales through these establishments. The objective of this study was to test two hypotheses about the etiology of these differential exposures based on theories of the economic geography of retail markets: (a) outlets will locate within or near areas of high alcohol demand, and (b) outlets will be excluded from areas with high land and structure rents. Data from the 2010 National Drug Strategy Household Survey were used to develop a surrogate for alcohol demand (i.e., market potential) at two census geographies for the city of Melbourne, Australia. Bayesian conditional autoregressive Poisson models estimated multilevel spatial relationships between counts of bars, restaurants, and off-premise outlets and market potential, income, and zoning ordinances (Level 1: n = 8,914). Market potentials were greatest in areas with larger older age, male, English-speaking, high-income populations. Independent of zoning characteristics, greater numbers of outlets appeared in areas with greater market potentials and the immediately surrounding areas. Greater income excluded outlets in local and surrounding areas. These findings are consistent with the hypothesis that alcohol outlets are located in areas with high demand and are excluded from high-income areas. These processes appear to take place at relatively small geographic scales, encourage the concentration of outlets in specific low-income areas, and represent a very general economic process likely to take place in communities throughout the world.

Prenatal Alcohol and Cocaine Exposure: Influences on Cognition, Speech, Language, and Hearing

ERIC Educational Resources Information Center

Cone-Wesson, B.

2005-01-01

This paper reviews research on the consequences of prenatal exposure to alcohol and cocaine on children's speech, language, hearing, and cognitive development. The review shows that cognitive impairment, learning disabilities, and behavioral disorders are the central nervous system manifestations of fetal alcohol syndrome (FAS), and cranio-facial…

Heterogeneity of p53 dependent genomic responses following ethanol exposure in a developmental mouse model of fetal alcohol spectrum disorder

PubMed Central

Mooney, Sandra M.; Middleton, Frank A.

2017-01-01

Prenatal ethanol exposure can produce structural and functional deficits in the brain and result in Fetal Alcohol Spectrum Disorder (FASD). In rodent models acute exposure to a high concentration of alcohol causes increased apoptosis in the developing brain. A single causal molecular switch that signals for this increase in apoptosis has yet to be identified. The protein p53 has been suggested to play a pivotal role in enabling cells to engage in pro-apoptotic processes, and thus figures prominently as a hub molecule in the intracellular cascade of responses elicited by alcohol exposure. In the present study we examined the effect of ethanol-induced cellular and molecular responses in primary somatosensory cortex (SI) and hippocampus of 7-day-old wild-type (WT) and p53-knockout (KO) mice. We quantified apoptosis by active caspase-3 immunohistochemistry and ApopTag™ labeling, then determined total RNA expression levels in laminae of SI and hippocampal subregions. Immunohistochemical results confirmed increased incidence of apoptotic cells in both regions in WT and KO mice following ethanol exposure. The lack of p53 was not protective in these brain regions. Molecular analyses revealed a heterogeneous response to ethanol exposure that varied depending on the subregion, and which may go undetected using a global approach. Gene network analyses suggest that the presence or absence of p53 alters neuronal function and synaptic modifications following ethanol exposure, in addition to playing a classic role in cell cycle signaling. Thus, p53 may function in a way that underlies the intellectual and behavioral deficits observed in FASD. PMID:28723918

Heterogeneity of p53 dependent genomic responses following ethanol exposure in a developmental mouse model of fetal alcohol spectrum disorder.

PubMed

Camargo Moreno, Maria; Mooney, Sandra M; Middleton, Frank A

2017-01-01

Prenatal ethanol exposure can produce structural and functional deficits in the brain and result in Fetal Alcohol Spectrum Disorder (FASD). In rodent models acute exposure to a high concentration of alcohol causes increased apoptosis in the developing brain. A single causal molecular switch that signals for this increase in apoptosis has yet to be identified. The protein p53 has been suggested to play a pivotal role in enabling cells to engage in pro-apoptotic processes, and thus figures prominently as a hub molecule in the intracellular cascade of responses elicited by alcohol exposure. In the present study we examined the effect of ethanol-induced cellular and molecular responses in primary somatosensory cortex (SI) and hippocampus of 7-day-old wild-type (WT) and p53-knockout (KO) mice. We quantified apoptosis by active caspase-3 immunohistochemistry and ApopTag™ labeling, then determined total RNA expression levels in laminae of SI and hippocampal subregions. Immunohistochemical results confirmed increased incidence of apoptotic cells in both regions in WT and KO mice following ethanol exposure. The lack of p53 was not protective in these brain regions. Molecular analyses revealed a heterogeneous response to ethanol exposure that varied depending on the subregion, and which may go undetected using a global approach. Gene network analyses suggest that the presence or absence of p53 alters neuronal function and synaptic modifications following ethanol exposure, in addition to playing a classic role in cell cycle signaling. Thus, p53 may function in a way that underlies the intellectual and behavioral deficits observed in FASD.

Alcohol effects on the epigenome in the germline: role in the inheritance of alcohol-related pathology

PubMed Central

Chastain, Lucy G.; Sarkar, Dipak K.

2017-01-01

Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown. Recent studies in animal models have suggested that epigenetic factors are also responsible for the transmission of alcohol-related pathologies across generations. Alcohol exposure has been shown to induce changes in the epigenome of sperm of exposed male animals, and these epimutations are inherited in the offspring. This paper reviews evidence for multigenerational and transgenerational epigenetic inheritance of alcohol-related pathology through the germline. We also review the literature on the epigenetic effects of alcohol exposure on somatic cells in brain, and its contribution to AUDs and FASDs. We note gaps in knowledge in this field, such as the lack of clinical studies in human populations and the lack of data on epigenetic inheritance via the female germline, and we suggest future research directions. PMID:28431793

Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process

PubMed Central

Walker, Brendan M.

2013-01-01

This article represents one of five contributions focusing on the topic “Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure” that were developed by awardees participating in the Young Investigator Award Symposium at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms. PMID:22459874

Characterization of Mouse Models of Early Pancreatic Lesions Induced by Alcohol and Chronic Pancreatitis.

PubMed

Xu, Shiping; Chheda, Chintan; Ouhaddi, Yassine; Benhaddou, Hajar; Bourhim, Mouloud; Grippo, Paul J; Principe, Daniel R; Mascariñas, Emman; DeCant, Brian; Tsukamoto, Hidekazu; Pandol, Stephen J; Edderkaoui, Mouad

2015-08-01

We describe the first mouse model of pancreatic intraepithelial neoplasia (PanIN) lesions induced by alcohol in the presence and absence of chronic pancreatitis. Pdx1-Cre;LSL-K-ras mice were exposed to Lieber-DeCarli alcohol diet for 6 weeks with cerulein injections. The PanIN lesions and markers of fibrosis, inflammation, histone deacetylation, epithelial-to-mesenchymal transition (EMT), and cancer stemness were measured by immunohistochemistry and Western. Exposure of Pdx1-Cre;LSL-K-ras mice to an alcohol diet significantly stimulated fibrosis and slightly but not significantly increased the level of PanIN lesions associated with an increase in tumor-promoting M2 macrophages. Importantly, the alcohol diet did not increase activation of stellate cells. Alcohol diet and cerulein injections resulted in synergistic and additive effects on PanIN lesion and M2 macrophage phenotype induction, respectively. Cerulein pancreatitis caused stellate cell activation, EMT, and cancer stemness in the pancreas. Pancreatitis caused histone deacetylation, which was promoted by the alcohol diet. Pancreatitis increased EMT and cancer stemness markers, which were not further affected by the alcohol diet. The results suggest that alcohol has independent effects on promotion of PDAC associated with fibrosis formed through a stellate cell-independent mechanism and that it further promotes early PDAC and M2 macrophage induction in the context of chronic pancreatitis.

Self-Reported Youth and Adult Exposure to Alcohol Marketing in Traditional and Digital Media: Results of a Pilot Survey.

PubMed

Jernigan, David H; Padon, Alisa; Ross, Craig; Borzekowski, Dina

2017-03-01

Alcohol marketing is known to be a significant risk factor for underage drinking. However, little is known about youth and adult exposure to alcohol advertising in digital and social media. This study piloted a comparative assessment of youth and adult recall of exposure to online marketing of alcohol. From September to October 2013, a pilot survey of past 30-day exposure to alcohol advertising and promotional content in traditional and digital media was administered to a national sample of 1,192 youth (ages 13 to 20) and 1,124 adults (ages ≥21) using a prerecruited Internet panel maintained by GfK Custom Research. The weighted proportions of youth and adults who reported this exposure were compared by media type and by advertising and promotional content. Youth were more likely than adults to recall exposure to alcohol advertising on television (69.2% vs. 61.9%), radio (24.8% vs. 16.7%), billboards (54.8% vs. 35.4%), and the Internet (29.7% vs. 16.8%), but less likely to recall seeing advertising in magazines (35.7% vs. 36.4%). Youth were also more likely to recall seeing advertisements and pictures on the Internet of celebrities using alcohol (36.1% vs. 20.8%) or wearing clothing promoting alcohol (27.7% vs. 15.9%), and actively respond (i.e., like, share, or post) to alcohol-related content online. Youth report greater exposure to alcohol advertising and promotional content than adults in most media, including on the Internet. These findings emphasize the need to assure compliance with voluntary industry standards on the placement of alcohol advertising and the importance of developing better tools for monitoring youth exposure to alcohol marketing, particularly on the Internet. Copyright © 2017 by the Research Society on Alcoholism.

Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo.

PubMed

Chuang, Cheng-Hung; Tsai, Cheng-Chih; Lin, En-Shyh; Huang, Chin-Shiu; Lin, Yun-Yu; Lan, Chuan-Ching; Huang, Chun-Chih

2016-10-31

The aim of the present study was to determine whether Lactobacillus salivarius (LS) and Lactobacillus johnsonii (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (γ-GT), lipid peroxidation, triglyceride (TG) and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA) levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo.

Focus on: epigenetics and fetal alcohol spectrum disorders.

PubMed

Kobor, Michael S; Weinberg, Joanne

2011-01-01

Epigenetic changes-stable but potentially reversible alterations in a cell's genetic information that result in changes in gene expression but do not involve changes in the underlying DNA sequence-may mediate some of the detrimental effects of prenatal alcohol exposure and contribute to the deficits and abnormalities associated with fetal alcohol spectrum disorders. These epigenetic processes are linked to the chromatin (i.e., DNA, histone proteins, and other associated proteins) and commonly involve chemical modifications (e.g., methylation) of these molecules, which may result in altered expression of the affected genes. Even alcohol exposure prior to conception appears to be able to induce epigenetic changes in the parental genetic material that can be passed on to the offspring and affect offspring outcome. Similarly, epigenetic processes may occur as a result of maternal alcohol consumption during the period between fertilization of the egg and implantation in the uterus. The period most sensitive to alcohol's adverse effects appears to be gastrulation, which corresponds to prenatal weeks 3 to 8 in the human and prenatal days 7 to 14 in the mouse, when cells are differentiating to form organs. One way in which alcohol exposure may induce epigenetic changes, particularly abnormal DNA methylation, is by affecting a set of biochemical reactions called the methionine-homocysteine cycle.

Peptidergic Agonists of Activity-Dependent Neurotrophic Factor Protect Against Prenatal Alcohol-Induced Neural Tube Defects and Serotonin Neuron Loss

PubMed Central

Zhou, Feng C.; Fang, Yuan; Goodlett, Charles

2009-01-01

Introduction Prenatal alcohol exposure via maternal liquid diet consumption by C57BL/6 (B6) mice causes conspicuous midline neural tube deficit (dysraphia) and disruption of genesis and development of serotonin (5-HT) neurons in the raphe nuclei, together with brain growth retardation. The current study tested the hypothesis that concurrent treatment with either an activity-dependent neurotrophic factor (ADNF) agonist peptide [SALLRSIPA, (SAL)] or an activity-dependent neurotrophic protein (ADNP) agonist peptide [NAPVSIPQ, (NAP)] would protect against these alcohol-induced deficits in brain development. Methods Timed-pregnant B6 dams consumed alcohol from embryonic day 7 (E7, before the onset of neurulation) until E15. Fetuses were obtained on E15 and brain sections processed for 5-HT immunocytochemistry, for evaluation of morphologic development of the brainstem raphe and its 5-HT neurons. Additional groups were treated either with SAL or NAP daily from E7 to E15 to assess the potential protective effects of these peptides. Measures of incomplete occlusion of the ventral canal and the frequency and extent of the openings in the rhombencephalon were obtained to assess fetal dysraphia. Counts of 5-HT-immunostained neurons were also obtained in the rostral and caudal raphe. Results Prenatal alcohol exposure resulted in abnormal openings along the midline and delayed closure of ventral canal in the brainstem. This dysraphia was associated with reductions in the number of 5-HT neurons both in the rostral raphe nuclei (that gives rise to ascending 5-HT projections) and in the caudal raphe (that gives rise to the descending 5-HT projections). Concurrent treatment of the alcohol-consuming dams with SAL prevented dysraphia and protected against the alcohol-induced reductions in 5-HT neurons in both the rostral and caudal raphe. NAP was less effective in protecting against dysraphia and did not protect against 5-HT loss in the rostral raphe, but did protect against loss in

Intestinal fungi contribute to development of alcoholic liver disease.

PubMed

Yang, An-Ming; Inamine, Tatsuo; Hochrath, Katrin; Chen, Peng; Wang, Lirui; Llorente, Cristina; Bluemel, Sena; Hartmann, Phillipp; Xu, Jun; Koyama, Yukinori; Kisseleva, Tatiana; Torralba, Manolito G; Moncera, Kelvin; Beeri, Karen; Chen, Chien-Sheng; Freese, Kim; Hellerbrand, Claus; Lee, Serene Ml; Hoffman, Hal M; Mehal, Wajahat Z; Garcia-Tsao, Guadalupe; Mutlu, Ece A; Keshavarzian, Ali; Brown, Gordon D; Ho, Samuel B; Bataller, Ramon; Stärkel, Peter; Fouts, Derrick E; Schnabl, Bernd

2017-06-30

Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin-like receptor CLEC7A on Kupffer cells and possibly other bone marrow-derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease.

Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes.

PubMed

Reynolds, James N; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2011-03-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. Copyright © 2011 Elsevier Inc. All rights reserved.

Fetal Alcohol Spectrum Disorders: Gene-Environment Interactions, Predictive Biomarkers, and the Relationship Between Structural Alterations in the Brain and Functional Outcomes

PubMed Central

Reynolds, James N.; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2016-01-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. PMID:21575841

Alcohol induces synaptotagmin 1 expression in neurons via activation of heat shock factor 1.

PubMed

Varodayan, F P; Pignataro, L; Harrison, N L

2011-10-13

Many synapses within the central nervous system are sensitive to ethanol. Although alcohol is known to affect the probability of neurotransmitter release in specific brain regions, the effects of alcohol on the underlying synaptic vesicle fusion machinery have been little studied. To identify a potential pathway by which ethanol can regulate neurotransmitter release, we investigated the effects of acute alcohol exposure (1-24 h) on the expression of the gene encoding synaptotagmin 1 (Syt1), a synaptic protein that binds calcium to directly trigger vesicle fusion. Syt1 was identified in a microarray screen as a gene that may be sensitive to alcohol and heat shock. We found that Syt1 mRNA and protein expression are rapidly and robustly up-regulated by ethanol in mouse cortical neurons, and that the distribution of Syt1 protein along neuronal processes is also altered. Syt1 mRNA up-regulation is dependent on the activation of the transcription factor heat shock factor 1 (HSF1). The transfection of a constitutively active Hsf1 construct into neurons stimulates Syt1 transcription, while transfection of Hsf1 small interfering RNA (siRNA) or a constitutively inactive Hsf1 construct into neurons attenuates the induction of Syt1 by ethanol. This suggests that the activation of HSF1 can induce Syt1 expression and that this may be a mechanism by which alcohol regulates neurotransmitter release during brief exposures. Further analysis revealed that a subset of the genes encoding the core synaptic vesicle fusion (soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor; SNARE) proteins share this property of induction by ethanol, suggesting that alcohol may trigger a specific coordinated adaptation in synaptic function. This molecular mechanism could explain some of the changes in synaptic function that occur following alcohol administration and may be an important step in the process of neuronal adaptation to alcohol. Copyright © 2011 IBRO. Published by

Epigenetic mechanisms in alcohol- and adversity-induced developmental origins of neurobehavioral functioning.

PubMed

Boschen, K E; Keller, S M; Roth, T L; Klintsova, A Y

The long-term effects of developmental alcohol and stress exposure are well documented in both humans and non-human animal models. Damage to the brain and attendant life-long impairments in cognition and increased risk for psychiatric disorders are debilitating consequences of developmental exposure to alcohol and/or psychological stress. Here we discuss evidence for a role of epigenetic mechanisms in mediating these consequences. While we highlight some of the common ways in which stress or alcohol impact the epigenome, we point out that little is understood of the epigenome's response to experiencing both stress and alcohol exposure, though stress is a contributing factor as to why women drink during pregnancy. Advancing our understanding of this relationship is of critical concern not just for the health and well-being of individuals directly exposed to these teratogens, but for generations to come. Copyright © 2018 Elsevier Inc. All rights reserved.

Associative DNA methylation changes in children with prenatal alcohol exposure.

PubMed

Laufer, Benjamin I; Kapalanga, Joachim; Castellani, Christina A; Diehl, Eric J; Yan, Liying; Singh, Shiva M

2015-01-01

Prenatal alcohol exposure (PAE) can cause fetal alcohol spectrum disorders (FASD). Previously, we assessed PAE in brain tissue from mouse models, however whether these changes are present in humans remains unknown. In this report, we show some identical changes in DNA methylation in the buccal swabs of six children with FASD using the 450K array. The changes occur in genes related to protocadherins, glutamatergic synapses, and hippo signaling. The results were found to be similar in another heterogeneous replication group of six FASD children. The replicated results suggest that children born with FASD have unique DNA methylation defects that can be influenced by sex and medication exposure. Ultimately, with future clinical development, assessment of DNA methylation from buccal swabs can provide a novel strategy for the diagnosis of FASD.

Socioeconomic Determinants of Exposure to Alcohol Outlets

PubMed Central

Morrison, Christopher; Gruenewald, Paul J.; Ponicki, William R.

2015-01-01

Objective: Alcohol outlets tend to be located in lower income areas, exposing lower income populations to excess risks associated with alcohol sales through these establishments. The objective of this study was to test two hypotheses about the etiology of these differential exposures based on theories of the economic geography of retail markets: (a) outlets will locate within or near areas of high alcohol demand, and (b) outlets will be excluded from areas with high land and structure rents. Method: Data from the 2010 National Drug Strategy Household Survey were used to develop a surrogate for alcohol demand (i.e., market potential) at two census geographies for the city of Melbourne, Australia. Bayesian conditional autoregressive Poisson models estimated multilevel spatial relationships between counts of bars, restaurants, and off-premise outlets and market potential, income, and zoning ordinances (Level 1: n = 8,914). Results: Market potentials were greatest in areas with larger older age, male, English-speaking, high-income populations. Independent of zoning characteristics, greater numbers of outlets appeared in areas with greater market potentials and the immediately surrounding areas. Greater income excluded outlets in local and surrounding areas. Conclusions: These findings are consistent with the hypothesis that alcohol outlets are located in areas with high demand and are excluded from high-income areas. These processes appear to take place at relatively small geographic scales, encourage the concentration of outlets in specific low-income areas, and represent a very general economic process likely to take place in communities throughout the world. PMID:25978830

Driving simulator sickness: Impact on driving performance, influence of blood alcohol concentration, and effect of repeated simulator exposures.

PubMed

Helland, Arne; Lydersen, Stian; Lervåg, Lone-Eirin; Jenssen, Gunnar D; Mørland, Jørg; Slørdal, Lars

2016-09-01

Simulator sickness is a major obstacle to the use of driving simulators for research, training and driver assessment purposes. The purpose of the present study was to investigate the possible influence of simulator sickness on driving performance measures such as standard deviation of lateral position (SDLP), and the effect of alcohol or repeated simulator exposure on the degree of simulator sickness. Twenty healthy male volunteers underwent three simulated driving trials of 1h's duration with a curvy rural road scenario, and rated their degree of simulator sickness after each trial. Subjects drove sober and with blood alcohol concentrations (BAC) of approx. 0.5g/L and 0.9g/L in a randomized order. Simulator sickness score (SSS) did not influence the primary outcome measure SDLP. Higher SSS significantly predicted lower average speed and frequency of steering wheel reversals. These effects seemed to be mitigated by alcohol. Higher BAC significantly predicted lower SSS, suggesting that alcohol inebriation alleviates simulator sickness. The negative relation between the number of previous exposures to the simulator and SSS was not statistically significant, but is consistent with habituation to the sickness-inducing effects, as shown in other studies. Overall, the results suggest no influence of simulator sickness on SDLP or several other driving performance measures. However, simulator sickness seems to cause test subjects to drive more carefully, with lower average speed and fewer steering wheel reversals, hampering the interpretation of these outcomes as measures of driving impairment and safety. BAC and repeated simulator exposures may act as confounding variables by influencing the degree of simulator sickness in experimental studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sex Differences in Early Postnatal Microglial Colonization of the Developing Rat Hippocampus Following a Single-Day Alcohol Exposure.

PubMed

Ruggiero, M J; Boschen, K E; Roth, T L; Klintsova, A Y

2018-06-01

Microglia are involved in various homeostatic processes in the brain, including phagocytosis, apoptosis, and synaptic pruning. Sex differences in microglia colonization of the developing brain have been reported, but have not been established following alcohol insult. Developmental alcohol exposure represents a neuroimmune challenge that may contribute to cognitive dysfunction prevalent in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. Most studies have investigated neuroimmune activation following adult alcohol exposure or following multiple exposures. The current study uses a single day binge alcohol exposure model (postnatal day [PD] 4) to examine sex differences in the neuroimmune response in the developing rat hippocampus on PD5 and 8. The neuroimmune response was evaluated through measurement of microglial number and cytokine gene expression at both time points. Male pups had higher microglial number compared to females in many hippocampal subregions on PD5, but this difference disappeared by PD8, unless exposed to alcohol. Expression of pro-inflammatory marker CD11b was higher on PD5 in alcohol-exposed (AE) females compared to AE males. After alcohol exposure, C-C motif chemokine ligand 4 (CCL4) was significantly increased in female AE pups on PD5 and PD8. Tumor necrosis factor-α (TNF-α) levels were also upregulated by AE in males on PD8. The results demonstrate a clear difference between the male and female neuroimmune response to an AE challenge, which also occurs in a time-dependent manner. These findings are significant as they add to our knowledge of specific sex-dependent effects of alcohol exposure on microglia within the developing brain.

Occupational Exposure to Alcohol-Based Hand Sanitizers: The Diagnostic Role of Alcohol Biomarkers in Hair.

PubMed

Salomone, A; Bozzo, A; Di Corcia, D; Gerace, E; Vincenti, M

2018-04-01

Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) in hair are effective direct biomarkers of ethanol ingestion, whose analytical determination can be used to discriminate between chronic and occasional ethanol intake. Ethanol is a compound widely used in some workplaces (e.g., clinics, hospitals) and is present in considerable amounts in mouthwash for oral cleaning, medications, cosmetic products, hydro-alcoholic disinfectants and antiseptics for hands. This study examined the ethyl alcohol exposure derived from hand disinfectants (in gel form) by simulating the typical occupational situation of medical-health workers (healthcare workers, nurses, surgeons, etc.) who frequently wash their hands with antiseptic sanitizer. Two types of hand disinfectants with 62% w/w of ethanol content were daily applied to the hands of a teetotaler for 20 times a day, for 4 consecutive weeks, thus simulating a typical workplace situation and a cumulative dermal exposure to ethanol of ~1,100 g. Different matrices (head, chest and beard hair, urine) were regularly sampled and analyzed using a ultra high-performance liquid chromatography tandem massspectrometry validated method for EtG and a (HS)SPME-GC-MS validated technique for FAEEs. The data obtained showed that a significant dermal absorption and/or inhalation of ethanol occurred, and that the use of detergents produce urinary EtG concentrations both higher than the cut-offs normally used for clinical and forensic analyses (either 100 and 500 ng/mL, depending on the context). The concentrations of the ethanol metabolites in the keratin matrices were, respectively, below the cut-off of 7 pg/mg for EtG and below 0.5 ng/mg for FAAEs (0.35 ng/mg for ethyl palmitate). In conclusion, the regular use of alcohol-based hand sanitizers can affect the concentration of urinary EtG and lead to positive analytical results, particularly when specimens are obtained shortly after sustained use of ethanol-containing hand sanitizer. On the

Invertebrate models of alcoholism.

PubMed

Scholz, Henrike; Mustard, Julie A

2013-01-01

For invertebrates to become useful models for understanding the genetic and physiological mechanisms of alcoholism related behaviors and the predisposition towards alcoholism, several general requirements must be fulfilled. The animal should encounter ethanol in its natural habitat, so that the central nervous system of the organism will have evolved mechanisms for responding to ethanol exposure. How the brain adapts to ethanol exposure depends on its access to ethanol, which can be regulated metabolically and/or by physical barriers. Therefore, a model organism should have metabolic enzymes for ethanol degradation similar to those found in humans. The neurons and supporting glial cells of the model organism that regulate behaviors affected by ethanol should share the molecular and physiological pathways found in humans, so that results can be compared. Finally, the use of invertebrate models should offer advantages over traditional model systems and should offer new insights into alcoholism-related behaviors. In this review we will summarize behavioral similarities and identified genes and mechanisms underlying ethanol-induced behaviors in invertebrates. This review mainly focuses on the use of the nematode Caenorhabditis elegans, the honey bee Apis mellifera and the fruit fly Drosophila melanogaster as model systems. We will discuss insights gained from those studies in conjunction with their vertebrate model counterparts and the implications for future research into alcoholism and alcohol-induced behaviors.

Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice.

PubMed

Ferrere, Gladys; Wrzosek, Laura; Cailleux, Frédéric; Turpin, Williams; Puchois, Virginie; Spatz, Madeleine; Ciocan, Dragos; Rainteau, Dominique; Humbert, Lydie; Hugot, Cindy; Gaudin, Françoise; Noordine, Marie-Louise; Robert, Véronique; Berrebi, Dominique; Thomas, Muriel; Naveau, Sylvie; Perlemuter, Gabriel; Cassard, Anne-Marie

2017-04-01

Alcoholic liver disease (ALD) is a leading cause of liver failure and mortality. In humans, severe alcoholic hepatitis is associated with key changes to intestinal microbiota (IM), which influences individual sensitivity to develop advanced ALD. We used the different susceptibility to ALD observed in two distinct animal facilities to test the efficiency of two complementary strategies (fecal microbiota transplantation and prebiotic treatment) to reverse dysbiosis and prevent ALD. Mice were fed alcohol in two distinct animal facilities with a Lieber DeCarli diet. Fecal microbiota transplantation was performed with fresh feces from alcohol-resistant donor mice to alcohol-sensitive receiver mice three times a week. Another group of mice received pectin during the entire alcohol consumption period. Ethanol induced steatosis and liver inflammation, which were associated with disruption of gut homeostasis, in alcohol-sensitive, but not alcohol resistant mice. IM analysis showed that the proportion of Bacteroides was specifically lower in alcohol-sensitive mice (p<0.05). Principal coordinate analysis showed that the IM of sensitive and resistant mice clustered differently. We targeted IM using two different strategies to prevent alcohol-induced liver lesions: (1) pectin treatment which induced major modifications of the IM, (2) fecal microbiota transplantation which resulted in an IM very close to that of resistant donor mice in the sensitive recipient mice. Both methods prevented steatosis, liver inflammation, and restored gut homeostasis. Manipulation of IM can prevent alcohol-induced liver injury. The IM should be considered as a new therapeutic target in ALD. Sensitivity to alcoholic liver disease (ALD) is driven by intestinal microbiota in alcohol fed mice. Treatment of mice with alcohol-induced liver lesions by fecal transplant from alcohol fed mice resistant to ALD or with prebiotic (pectin) prevents ALD. These findings open new possibilities for treatment of human

Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

PubMed

Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

2015-01-02

Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish. Copyright © 2014 Elsevier Inc. All rights reserved.

May alcohol-induced increase of HDL be considered as atheroprotective?

PubMed

Králová Lesná, I; Suchánek, P; Stávek, P; Poledne, R

2010-01-01

It is well known that the consumption of moderate doses of alcohol leads to the increase of HDL-cholesterol (HDL-C). Atheroprotectivity of HDL particles is based primarily on their role in reverse cholesterol transport (RCT). In the study with a cross-over design 13 male volunteers were studied in two different regimens: i) drinking of 36 g alcohol daily and ii) drinking only non-alcoholic beverages, to test whether alcohol-induced increase of HDL cholesterol can affect cholesterol efflux (CHE) from cell culture of labeled human macrophages. Alcohol consumption induced significant (p < 0.05) increases of HDL cholesterol from 1.25 +/- 0.32 to 1.34 +/- 0.38 mmol/l and Apo A1 from 1.34 +/- 0.16 to 1.44 +/- 0.19 g/l. These changes were combined with a slight increase of cholesterol efflux from 13.8 +/- 2.15 to 14.9 +/- 1.85 % (p = 0.059). There were significant correlations between individual changes of HDL-C and Apo A1 concentrations and individual changes of CHE (0.51 and 0.60, respectively). In conclusion, moderate alcohol consumption changes the capacity of plasma to induce CHE only at a border line significance.

Autophagy in Alcohol-Induced Multiorgan Injury: Mechanisms and Potential Therapeutic Targets

PubMed Central

Wang, Shaogui; Ni, Hong-Min; Huang, Heqing

2014-01-01

Autophagy is a genetically programmed, evolutionarily conserved intracellular degradation pathway involved in the trafficking of long-lived proteins and cellular organelles to the lysosome for degradation to maintain cellular homeostasis. Alcohol consumption leads to injury in various tissues and organs including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury in most tissues but could be detrimental in heart and muscle. This review summarizes current knowledge about the role of autophagy in alcohol-induced injury in different tissues/organs and its potential molecular mechanisms as well as possible therapeutic targets based on modulation of autophagy. PMID:25140315

Effect of alcohol exposure on fetal brain development

NASA Astrophysics Data System (ADS)

Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

2013-02-01

Alcohol consumption during pregnancy can be severely damage to the brain development in fetuses. This study investigates the effects of maternal ethanol consumption on brain development in mice embryos. Pregnant mice at gestational day 12.5 were intragastrically gavaged with ethanol (3g/Kg bwt) twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and fixed in 4% paraformaldehyde and imaged using a swept-source optical coherence tomography (SSOCT) system. 3D images of the mice embryo brain were obtained and the volumes of the left and right ventricles of the brain were measured. The average volumes of the left and the right volumes of 5 embryos each alcohol-exposed and control embryos were measured to be 0.35 and 0.15 mm3, respectively. The results suggest that the left and right ventricle volumes of brain are much larger in the alcohol-exposed embryos as compared to control embryos indicating alcohol-induced developmental delay.

Alcohol Misuse in Reserve Soldiers and their Partners: Cross-Spouse Effects of Deployment and Combat Exposure.

PubMed

Vest, Bonnie M; Heavey, Sarah Cercone; Homish, D Lynn; Homish, Gregory G

2018-04-16

Military deployment and combat are associated with worse outcomes, including alcohol misuse. Less is known about how these experiences affect soldiers' spouses. The study objective was to explore relationships between deployment, combat exposure, and alcohol misuse; especially cross-spouse effects (effect of one partner's experiences/behavior on the other partner), which has been under-examined in military samples. U.S. Army Reserve/National Guard soldiers and their partners completed a questionnaire covering physical and mental health, military service and substance use. Negative binomial regression models examined number of deployments and combat exposure individually for alcohol misuse and frequent heavy drinking (FHD). In additional models, we examined combat exposure's role on alcohol outcomes, controlling for the soldiers' number of deployments, PTSD symptoms, age, and in cross-spouse models, alcohol use and FHD. We considered individuals' deployment experiences related to their alcohol outcomes and to their spouses' alcohol outcomes. The study sample included male soldiers with current/lifetime military service (n = 248) and their female partners. Combat exposure was related to FHD (RR: 1.01, p < .05, 95% CI: 1.01, 1.01) among male soldiers while controlling for PTSD symptoms, number of deployments, and age. Female partners of male soldiers were more likely to engage in FHD (RR: 1.01, p < .05, 95% CI: 1.01, 1.01) if their spouse experienced combat. Our results demonstrate that male soldiers and their spouses are at increased risk of FHD if the soldier experienced combat. This points to the need for better screening, particularly of spouses of soldiers, whose alcohol misuse may be overlooked.

Alcoholic and non-alcoholic steatohepatitis

PubMed Central

Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

2015-01-01

This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice.

PubMed

Zhou, Tong; Zhang, Yu-Jie; Xu, Dong-Ping; Wang, Fang; Zhou, Yue; Zheng, Jie; Li, Ya; Zhang, Jiao-Jiao; Li, Hua-Bin

2017-01-01

Chronic excessive alcohol consumption (more than 40-80 g/day for males and more than 20-40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

The 2008-2009 recession and alcohol outcomes: differential exposure and vulnerability for Black and Latino populations.

PubMed

Zemore, Sarah E; Mulia, Nina; Jones-Webb, Rhonda J; Liu, Huiguo; Schmidt, Laura

2013-01-01

We examined whether race/ethnicity was related to exposure to acute economic losses in the 2008-2009 recession, even accounting for individual-level and geographic variables, and whether it influenced associations between economic losses and drinking patterns and problems. Data were from the 2010 National Alcohol Survey (N = 5,382). Surveys assessed both severe losses (i.e., job and housing loss) and moderate losses (i.e., reduced hours/pay and trouble paying the rent/mortgage) attributed to the 2008-2009 recession. Alcohol outcomes included total annual volume, monthly drunkenness, drinking consequences, and alcohol dependence (based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Compared with Whites, Blacks reported significantly greater exposure to job loss and trouble paying the rent/mortgage, and Latinos reported greater exposure to all economic losses. However, only Black-White differences were robust in multivariate analyses. Interaction tests suggested that associations between exposure to economic loss and alcohol problems were stronger among Blacks than Whites. Given severe (vs. no) loss, Blacks had about 13 times the odds of both two or more drinking consequences and alcohol dependence, whereas the corresponding odds ratios for Whites were less than 3. Conversely, associations between economic loss and alcohol outcomes were weak and ambiguous among Latinos. Results suggest greater exposure to economic loss for both Blacks and Latinos (vs. Whites) and that the Black population may be particularly vulnerable to the negative effects of economic hardship on the development and/or maintenance of alcohol problems. Findings extend the economic literature and signal policy makers and service providers that Blacks and Latinos may be at special risk during economic downturns.

Prenatal alcohol exposure and childhood balance ability: findings from a UK birth cohort study

PubMed Central

Humphriss, Rachel; Hall, Amanda; May, Margaret; Zuccolo, Luisa; Macleod, John

2013-01-01

Objective To investigate the association of prenatal alcohol exposure with balance in10-year-old children. Design Population-based prospective longitudinal study. Setting Former Avon region of UK (Southwest England). Participants 6915 children from the Avon Longitudinal Study of Parents and Children who had a balance assessment at age 10 and had data on maternal alcohol consumption. Outcome measures 3 composite balance scores: dynamic balance (beam-walking), static balance eyes open, static balance eyes closed (heel-to-toe balance on a beam and standing on one leg, eyes open or closed). Results Most mothers (95.5%) consumed no-to-moderate amounts (3–7 glasses/week) of alcohol during pregnancy. Higher total-alcohol consumption was associated with maternal-social advantage, whereas binge drinking (≥4 units/day) and abstinence were associated with maternal social disadvantage. No evidence was found of an adverse effect of maternal-alcohol consumption on childhood balance. Higher maternal-alcohol use during pregnancy was generally associated with better offspring outcomes, with some specific effects appearing strong (static balance eyes open and moderate total alcohol exposure at 18 weeks, adjusted OR 1.23 (95% CI 1.01 to 1.49); static balance eyes closed and moderate total alcohol exposure at 18 weeks, adjusted OR 1.25 (95% CI 1.06 to 1.48). Similar results were found for both paternal and postnatal maternal alcohol exposure. A Mendelian-randomization approach was used to estimate the association between maternal genotype and offspring balance using the non-synonymous variant rs1229984*A (ADH1B) to proxy for lower maternal alcohol consumption; no strong associations were found between this genotype/proxy and offspring balance. Conclusions No evidence was found to indicate that moderate maternal alcohol consumption in this population sample had an adverse effect on offspring balance at age 10. An apparent beneficial effect of higher total maternal alcohol

Alcohol- and light-induced electro-oculographic responses: variability and clinical utility.

PubMed

Marmor, Michael F; Wu, Kathy H C

2005-01-01

The alcohol-induced electro-oculographic (EOG) response has been proposed by Arden as an indicator of retinal pigment epithelial (RPE) integrity. We have evaluated the consistency of the alcohol-EOG with respect to clinical applicability and compared this response to the ISCEV-standard EOG. We recorded, in a group of normal subjects (n=29, 14 men with mean age 42+/-11 years and 15 women with mean age 36+/-13 years), the alcohol response to a single oral dose of ethanol at 160 mg/kg (as 40 proof vodka, drunk in 15 s after 12 h of fasting), followed by an ISCEV-standard EOG 90 min after alcohol administration. Blood alcohol levels were monitored at regular intervals with a breath analyzer. We found a wide range of amplitudes in both light and alcohol responses among participants, from minimal to large values. Subjects had a wide range of blood alcohol concentrations from 0.02 to 0.10%; near the time of the response peak, but there was no relationship between alcohol levels and peak/baseline ratios. In addition, there was no relationship between alcohol peak/baseline ratio and the Arden ratio. Neither the alcohol nor the light response parameters showed any relationship with age or gender. Some of the inter-individual variability in the EOG response to alcohol may reflect variable absorption of oral alcohol. The alcohol-induced EOG has too broad a range of responses to be useful clinically for the one-time evaluation of individual patients. We have similar concerns regarding clinical applications of the standard light-induced EOG.

Effects of childhood exposure to familial alcoholism and family violence on adolescent substance use, conduct problems, and self-esteem.

PubMed

Ritter, Jennifer; Stewart, Michael; Bernet, Christine; Coe, Michael; Brown, Sandra A

2002-04-01

Exposure to familial alcoholism has been associated with many behavioral and emotional difficulties among offspring. However, few studies have examined environmental risks that often coexist with familial alcoholism, and which may influence the development of offspring psychosocial problems. This study examined potential additive and interactive effects of childhood exposure to family violence and childhood exposure to familial alcoholism on adolescent functioning. Three domains of adolescent functioning were examined in a high-risk community sample of 109 families: lifetime levels of substance use, conduct disorder behaviors, and self-esteem. Results indicated that both childhood exposure to familial alcoholism and childhood exposure to family violence were associated with psychosocial functioning of offspring during adolescence, although the relations differ according to domain of functioning and gender.