Individual differences in the engagement of habitual control over alcohol seeking predicts the development of compulsive alcohol seeking and drinking

AbstractExcessive drinking is an important behavioural characteristic of alcohol addiction, but not the only one. Individuals addicted to alcohol crave alcoholic beverages, spend time seeking alcohol despite negative consequences, and eventually drink to intoxication. With prolonged use, control over alcohol seeking devolves to anterior dorsolateral striatum, dopamine-dependent mechanisms implicated in habit learning and individuals in whom alcohol-seeking relies more on these mechanisms are more likely to persist in seeking alcohol despite the risk of punishment. Here, we tested the hypothesis that the development of habitual alcohol-seeking predicts the development of compulsive seeking and that, once developed, it is associated with compulsive alcohol drinking. Male alcohol-preferring rats were pre-exposed intermittently to a two-bottle choice procedure, and trained on a seeking–taking chained schedule of alcohol reinforcement until some individuals developed punishment-resistant seeking behaviour. The associative basis of their seeking responses was probed with an outcome-devaluation procedure, early or late in training. After seeking behaviour was well established, subjects that had developed greater resistance to outcome-devaluation (were more habitual) were more likely to show punishment-resistant (compulsive) alcohol seeking. These individuals also drank more alcohol, despite quinine adulteration, even though having similar alcohol preference and intake before and during instrumental training. They were also less sensitive to changes in the contingency between seeking responses and alcohol outcome, providing further evidence of recruitment of the habit system. We therefore provide direct behavioural evidence that compulsive alcohol seeking emerges alongside compulsive drinking in individuals that have preferentially engaged the habit system.

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A molecular mechanism for choosing alcohol over an alternative reward

Science ◽

10.1126/science.aao1157 ◽

2018 ◽

Vol 360 (6395) ◽

pp. 1321-1326 ◽

Cited By ~ 66

Author(s):

Eric Augier ◽

Estelle Barbier ◽

Russell S. Dulman ◽

Valentina Licheri ◽

Gaëlle Augier ◽

...

Keyword(s):

Molecular Mechanism ◽

Alcohol Addiction ◽

Aminobutyric Acid ◽

Central Amygdala ◽

Choice Preference ◽

Choice Procedure ◽

Sweet Solution ◽

High Motivation ◽

Exclusive Choice ◽

Alcohol Dependent

Alcohol addiction leads to increased choice of alcohol over healthy rewards. We established an exclusive choice procedure in which ~15% of outbred rats chose alcohol over a high-value reward. These animals displayed addiction-like traits, including high motivation to obtain alcohol and pursuit of this drug despite adverse consequences. Expression of the γ-aminobutyric acid (GABA) transporter GAT-3 was selectively decreased within the amygdala of alcohol-choosing rats, whereas a knockdown of this transcript reversed choice preference of rats that originally chose a sweet solution over alcohol. GAT-3 expression was selectively decreased in the central amygdala of alcohol-dependent people compared to those who died of unrelated causes. Impaired GABA clearance within the amygdala contributes to alcohol addiction, appears to translate between species, and may offer targets for new pharmacotherapies for treating this disorder.

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A Study on Effectiveness of Community De-Addiction Camp at Chamarajanagar

Asian Review of Social Sciences ◽

10.51983/arss-2019.8.1.1506 ◽

2019 ◽

Vol 8 (1) ◽

pp. 132-137

Author(s):

Suman K. Murthy

Keyword(s):

Addiction Treatment ◽

Positive Impact ◽

Participant Observation ◽

Total Duration ◽

T Test ◽

Alcohol Addiction ◽

Community Level ◽

Negative Consequences ◽

Significant Difference ◽

The Impact

Alcohol addiction is a serious health hazard which has negative consequences for the affected individual as well as his family and community. Inpatient based de addiction treatment is commonly seen to tackle the problem of addiction. Of late, Community de addiction camps are providing de addiction treatment at community level in India. The current study looks into the impact of exposure to community de addiction camp organized by SKDRDP, Chamarajanagar, Karnataka State, India. Qualitative experimental research design is adopted to study the impact of exposure to the community de addiction camp. The total duration of the residential community de addiction camp was eight days. The universe for the study comprised of 103 participants attending the community de addiction camp. 40 participants formed the sample. Tools used for gathering the data were WHO-AUDIT, Interview schedule and participant observation. The data were analysed using paired t- test using SPSS version version 22.0 and participant observation recordings. The community de addiction camp has met all the thirteen expectations of the participants with regard to the camp; The result of t-test found that there is statistically significant difference in the mean scores on all parameters between before and after de addiction camp; there exists significant positive relationship between Clint behavior and client participation before the community de addiction camp. The participants had a positive impact from the exposure to the camp, which was evident to the researchers who were participant observers of the whole process. The community de addiction camp has been successful in bringing about a positive impact on the participants during the conduct of the camp and abstinence was 100% at 1 month post camp follow up. In view of these findings, the current study concludes that community de addiction camps have a positive impact on the participants. Community de addiction camps are an effective and economical way to combat alcohol addiction at the community level.

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mTORC1 in the orbitofrontal cortex promotes habitual alcohol seeking

eLife ◽

10.7554/elife.51333 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 6

Author(s):

Nadege Morisot ◽

Khanhky Phamluong ◽

Yann Ehinger ◽

Anthony L Berger ◽

Jeffrey J Moffat ◽

...

Keyword(s):

Orbitofrontal Cortex ◽

Heavy Alcohol ◽

Mechanistic Target Of Rapamycin ◽

Heavy Alcohol Use ◽

Habitual Behavior ◽

Habitual Responding ◽

Mtorc1 Activation ◽

Outcome Devaluation ◽

Alcohol Seeking ◽

Alcohol Dependent

The mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in dendritic translation and in learning and memory. We previously showed that heavy alcohol use activates mTORC1 in the orbitofrontal cortex (OFC) of rodents (Laguesse et al., 2017a). Here, we set out to determine the consequences of alcohol-dependent mTORC1 activation in the OFC. We found that inhibition of mTORC1 activity in the OFC attenuates alcohol seeking and restores sensitivity to outcome devaluation in rats that habitually seek alcohol. In contrast, habitual responding for sucrose was unaltered by mTORC1 inhibition, suggesting that mTORC1’s role in habitual behavior is specific to alcohol. We further show that inhibition of GluN2B in the OFC attenuates alcohol-dependent mTORC1 activation, alcohol seeking and habitual responding for alcohol. Together, these data suggest that the GluN2B/mTORC1 axis in the OFC drives alcohol seeking and habit.

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Policy Implications of the WHO Strategy to Reduce the Harmful Use of Alcohol

SUCHT - Zeitschrift für Wissenschaft und Praxis / Journal of Addiction Research and Practice ◽

10.1024/0939-5911.a000099 ◽

2011 ◽

Vol 57 (2) ◽

pp. 85-98 ◽

Cited By ~ 4

Author(s):

Peter Anderson

Keyword(s):

Health Impact ◽

Community Action ◽

Policy Implications ◽

Alcoholic Beverages ◽

World Health ◽

Supporting Evidence ◽

Negative Consequences ◽

Minimum Age ◽

Harmful Use ◽

Harmful Use Of Alcohol

Aims: To describe the supporting evidence and policy implications of the 10 target areas of the WHO strategy to reduce the harmful use of alcohol. Methods: Based on published systematic reviews of the literature and publications of the World Health Organization, the supporting evidence and policy implications of the 10 target areas are described. Findings: There is evidence to support action in each of the 10 target areas: leadership, awareness and commitment; health services’ response; community action; drink-driving policies; availability of alcohol; marketing of alcoholic beverages; pricing policies; reducing the negative consequences of intoxication; reducing the public health impact of illegal and informal alcohol; and monitoring and surveillance. Conclusions: The following policy measures have the strongest evidence: increasing alcohol taxes; government monopolies for the retail sale of alcohol; restricting the density of outlets and the days and hours of sale; increasing the minimum age of purchase; lowering the legal BAC levels for driving; introducing random breath-testing for driving; implementing widespread brief advice for hazardous and harmful alcohol consumption; and ensuring treatment for alcohol use disorders. There is reasonable evidence to support the introduction of a minimum price per gram of alcohol; restricting the volume of commercial communications; and enforcing the restrictions of sales to intoxicated and under-age people.

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Actions of Alcohol in Brain: Genetics, Metabolomics, GABA Receptors, Proteomics and Glutamate Transporter GLAST/EAAT1

Current Molecular Pharmacology ◽

10.2174/1874467213666200424155244 ◽

2020 ◽

Vol 14 (2) ◽

pp. 138-149 ◽

Cited By ~ 1

Author(s):

Mohammed Abul Kashem ◽

Omar Šerý ◽

David V. Pow ◽

Benjamin D. Rowlands ◽

Caroline D. Rae ◽

...

Keyword(s):

Energy Metabolism ◽

Gaba Receptors ◽

Glutamate Transporter ◽

Alcohol Addiction ◽

Post Mortem ◽

Chronic Alcohol ◽

Excessive Drinking ◽

Gaba A ◽

Brain Energy

We present an overview of genetic, metabolomic, proteomic and neurochemical studies done mainly in our laboratories that could improve prediction, mechanistic understanding and possibly extend to diagnostics and treatment of alcoholism and alcohol addiction. Specific polymorphisms in genes encoding for interleukins 2 and 6, catechol-O-methyl transferase (COMT), monaminooxidase B (MAO B) and several other enzymes were identified as associated with altered risks of alcoholism in humans. A polymorphism in the gene for BDNF has been linked to the risk of developing deficiences in colour vision sometimes observed in alcoholics. Metabolomic studies of acute ethanol effects on guinea pig brain cortex in vitro, lead to the identification of specific subtypes of GABA(A) receptors involved in the actions of alcohol at various doses. Acute alcohol affected energy metabolism, oxidation and the production of actaldehyde and acetate; this could have specific consequences not only for the brain energy production/utilization but could influence the cytotoxicity of alcohol and impact the epigenetics (histone acetylation). It is unlikely that brain metabolism of ethanol occurs to any significant degree; the reduction in glucose metabolism following alcohol consumption is due to ethanol effects on receptors, such as α4β3δ GABA(A) receptors. Metabolomics using post-mortem human brain indicated that the catecholaminergic signalling may be preferentially affected by chronic excessive drinking. Changes in the levels of glutathione were consistent with the presence of severe oxidative stress. Proteomics of the post-mortem alcoholic brains identified a large number of proteins, the expression of which was altered by chronic alcohol, with those associated with brain energy metabolism among the most numerous. Neurochemical studies found the increased expression of glutamate transporter GLAST/EAAT1 in brain as one of the largest changes caused by alcoholism. Given that GLAST/EAAT1 is one of the most abundant proteins in the nervous tissue and is intimately associated with the function of the excitatory (glutamatergic) synapses, this may be among the most important effects of chronic alcohol on brain function. It has so far been observed mainly in the prefrontal cortex. We show several experiments suggesting that acute alcohol can translocate GLAST/EAAT1 in astrocytes towards the plasma membrane (and this effect is inhibited by the GABA(B) agonist baclofen) but neither the mechanism nor the specificity (to alcohol) of this phenomenon have been established. Furthermore, as GLAST/EAAT1 is also expressed in testes and sperm (and could also be affected there by chronic alcohol), the levels of GLAST/EAAT1 in sperm could be used as a diagnostic tool in testing the severity of alcoholism in human males. We conclude that the reviewed studies present a unique set of data which could help to predict the risk of developing alcohol dependence (genetics), to improve the understanding of the intoxicating actions of alcohol (metabolomics), to aid in assessing the extent of damage to brain cells caused by chronic excessive drinking (metabolomics and proteomics) and to point to molecular targets that could be used in the treatment and diagnosis of alcoholism and alcohol addiction.

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Anthropological aspects of alcoholic drinks consumption in the Mediterranean culture / Aspectos antropológicos del consumo de bebidas alcohólicas en las culturas mediterráneas

Health and Addictions/Salud y Drogas ◽

10.21134/haaj.v7i2.73 ◽

2007 ◽

Vol 7 (2) ◽

Author(s):

Francisco Pascual Pastor

Keyword(s):

Young People ◽

Alcohol Abuse ◽

Life Style ◽

European Countries ◽

Alcoholic Beverages ◽

Negative Consequences ◽

Religious Rituals ◽

Mediterranean Culture ◽

Alcoholic Drinks ◽

Sobre Todo

El consumo de bebidas alcohólicas se ha convertido a lo largo de los siglos en un hecho cotidiano, con distintas implicaciones y motivaciones, se ha utilizado como alimento, medicamento o en el rituales mágico religiosos de distintas culturas.Pero también es verdad que los abusos del mismo han producido una serie de complicaciones tanto en la salud física como psicológica de aquellos que han utilizado el etanol de forma desproporcionada.Pero desde el efecto relajante – desinhibidor a la implicación económica y sus múltiples consecuencia ha provocado que aparezcan una serie de ambivalencias, unas proclives al consumo otras proclives a la restricción del mismo.Sea como fuere, tanto en España, como en los distintos países de las culturas mediterráneas y ahora por extensión en otros países de Europa el consumo de bebidas alcohólicas y todo lo que ello comporta ha condicionado poderosamente los estilos y formas de vivir.El uso cotidiano, el consumo de fin de semana y los atracones estánpresentes e incluso las edades de inicio van disminuyendo y las cantidades consumidas se van incrementando, obviando en gran manera las consecuencias negativas de los consumos abusivos.Cultura, tradición y forma de ser conforman un estilo de vida en el que las bebidas alcohólicas están omnipresentes.La última consideración es la necesidad de regular la oferta y lademanda sobre todo entre los jóvenes. AbstractThe alcoholic beverages consumption has become across the centuries in a daily fact, with different implications and motivations, it has been used as well as food and medicine in magical and religious rituals in different cultures.But alcohol abuse has produced a lot of physical, social and psychological complications in drinkers too.Multiple consequences and ambivalences appear caused by relaxingand economical effects. The ambivalences have favoured both the consumption and the restriction.Anyway, in Spain and in other Mediterranean and European countries, alcoholic drinks have determined styles and forms of life.The usual consumption, the weekend use and abuse and the bingedrinking are present in youngsters. The starting age is decreasing and the consumption is increasing. The abuse negative consequences have been avoided.Culture, tradition and way of being conform a special life style where the spirits are omnipresent.The last consideration, it is necessary to regulate the offer and demand of spirits mainly between young people.

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Alcohol Seeking Under Risk of Punishment Is Associated With Activation of Cortical and Subcortical Brain Regions

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.739681 ◽

2021 ◽

Vol 15 ◽

Author(s):

Allison J. McDonald ◽

Isis Alonso-Lozares ◽

Vasco Rauh ◽

Yvar van Mourik ◽

Dustin Schetters ◽

...

Keyword(s):

Discriminative Stimulus ◽

Discrimination Task ◽

Brain Regions ◽

Male Rats ◽

Negative Consequences ◽

Self Administration ◽

Higher Alcohol ◽

Cortical Regions ◽

Alcohol Seeking ◽

Motivational Conflict

In humans, stimuli associated with alcohol availability can provoke relapse during abstinence. In this study, we investigated the role of discriminative stimuli (DS) in the control of alcohol seeking in two types of behavioral tests. The first test examined the ability of an alcohol-associated DS to promote alcohol seeking (relapse) after punishment-imposed abstinence in the presence of a different DS. Following this, we tested whether the differentially associated DS can promote and suppress alcohol self-administration in a within-session discrimination task. During the within-session discrimination task, we also tested the rate of alcohol self-administration when two DS are presented in a compound. We first trained Long-Evans male rats (n = 24) to self-administer alcohol in the presence of one DS (reward-associated discriminative stimulus, rewDS) and then punished that behavior in the presence of a different DS (punishment-associated discriminative stimulus, punDS). On the test, we found that rats tested with the rewDS showed higher alcohol seeking than rats tested with the punDS. This result shows that a single Cue DS can promote alcohol seeking in a manner comparable to contexts. Subsequently, we trained 16 of these rats in a within-session trial-based discrimination task, comprised of intervening 2-min trials of rewDS, punDS, or conflict with rewDS and punDS in compound and a reduced probability of punishment. We found that alcohol self-administration is bi-directionally regulated by the rewDS and punDS. In conflict trials, alcohol self-administration was at a rate that was intermediate between the rewDS and punDS trials. In a final test, rats were presented with one of the three trial conditions and perfused for Fos immunohistochemistry. We found Fos expression was higher in the rats tested in the conflict condition in three interconnected sub-cortical brain regions. This study demonstrated the important role that alcohol-associated DS plays an important role in promoting relapse to alcohol seeking after punishment-imposed abstinence. We also implemented a within-session discrimination task that allows for the study of alcohol seeking under motivational conflict, which may be relevant for alcohol use despite negative consequences. The results from the Fos data suggest that higher alcohol seeking in approach-avoidance motivational conflict is associated with activation of sub-cortical regions but not cortical regions.

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Alcohol preferring P rats exhibit aversion resistant drinking of alcohol adulterated with quinine

10.1101/689919 ◽

2019 ◽

Author(s):

Nicholas M. Timme ◽

David Linsenbardt ◽

Maureen Timm ◽

Taylor Galbari ◽

Ethan Cornwell ◽

...

Keyword(s):

Alcohol Consumption ◽

Genetic Risk ◽

Alcohol Use Disorder ◽

Home Cage ◽

Bitter Taste ◽

Negative Consequences ◽

Excessive Drinking ◽

Alcohol Access ◽

Future Work ◽

Quinine Solution

AbstractUnderstanding why some people continue to drink alcohol despite negative consequences and others do not is a central problem in the study of alcohol use disorder (AUD). In this study, we used alcohol preferring P rats (a strain bred to prefer to drink alcohol, a model for genetic risk for AUD) and Wistars (control) to examine drinking despite negative consequences in the form of an aversive bitter taste stimuli produced by quinine. Animals were trained to consume 10% ethanol in a simple Pavlovian conditioning task that paired alcohol access with an auditory stimulus. When the alcohol was adulterated with quinine (0.1 g/L), P rats continued to consume alcohol+quinine at the same rate as unadulterated alcohol, despite a demonstrated aversion to quinine adulterated alcohol when given a choice between adulterated and unadulterated alcohol in the home cage. Conversely, Wistars decreased consumption of quinine adulterated alcohol in the task, but continued to try the alcohol+quinine solution at similar rates to unadulterated alcohol. These results indicate that following about 8 weeks of alcohol consumption P rats exhibit aversion resistant drinking. This model could be used in future work to explore how biological basis of alcohol consumption and genetic risk for excessive drinking lead to drinking that is resistant to devaluation.

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On Some Names of Braga and Moonshine in Northern Russian Dialects

Vestnik Volgogradskogo gosudarstvennogo universiteta Serija 2 Jazykoznanije ◽

10.15688/jvolsu2.2020.4.3 ◽

2020 ◽

pp. 29-41

Author(s):

Ksenia Osipova

Keyword(s):

Alcohol Addiction ◽

Alcoholic Beverages ◽

Economic Factors ◽

Russian North ◽

Social Demographic

The article represents the description of the group of homemade alcoholic beverages names, which exist in the dialects of Arkhangelsk, Vologda and Kostroma regions. The study is based on lexical materials of the oponymic Expedition of the Ural University, as well as dialect dictionaries, which include the lexemes used on the territory of the Russian North. The peculiarities of vocabulary formation and the influence of social, demographic and economic factors on its formation are revealed. Semantic-motivational and etymological analysis of dialectal lexemes showed that this group of vocabulary, along with the original Northern Russian units, includes borrowings from Volga dialects, semi-professional languages and the words originating from foreign sources (polonism, turkism). The author identified sustained motivational models presented in the considered nominations: the semantics of "homemade intoxicating drink" emerges from the alteration of meanings "low-quality liquid"; "disorder, bustle", "prank, hooligan"; "talk, chatter". The peculiarities of this lexical group were influenced by governmental bans on home brewing: there are a large number of euphemisms and variability of the lexical group. Compared with beer, home brew and moonshine in the Russian North were considered second-rate drinks and were associated with alcohol addiction, while drinking beer rarely caused social condemnation.

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Alcohol mortality in Russia: assessment with representative survey data

Population and Economics ◽

10.3897/popecon.4.e51653 ◽

2020 ◽

Vol 4 (3) ◽

pp. 75-95

Author(s):

Polina O. Kuznetsova

Keyword(s):

Alcohol Consumption ◽

Life Expectancy ◽

Premature Mortality ◽

Alcoholic Beverages ◽

Negative Consequences ◽

Excessive Alcohol Consumption ◽

Men And Women ◽

Relative Risks ◽

Excessive Alcohol ◽

External Causes

According to vast empirical evidence, excessive alcohol consumption is an important factor of premature mortality in Russia. At the same time, quantifying alcohol-related deaths is not so easy, as generally the discussion of alcohol mortality only concerns the causes of death attributed solely to alcohol, which significantly narrows the range of possible negative consequences. Including data on losses from myocardial infarction, coronary heart disease and other common cardiovascular and other diseases in alcohol mortality estimates is enabled by an approach using data on the relative risks of death from various causes depending on the type of alcohol consumption. Within this study, alcohol consumption, depending on sex and age, was assessed on data from a representative national survey, taking into account information on the volume of recorded sales of alcoholic beverages. According to the obtained results, in 2018 the death rate from alcohol-related causes in Russia amounted to 196,000 people, 146,000 men and 50,000 women among them. The peak of alcohol mortality is observed among people aged over 50. The structure of alcohol mortality is dominated by diseases of the cardiovascular system and external causes, and for men the contribution of external causes is significantly higher. Excessive alcohol consumption reduces life expectancy by 5.9 and 4.7 years for men and women, and healthy life expectancy by 4.2 and 2.6 years for men and women.

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