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    Gut Microbiota‐Derived Extracellular Vesicles Influence Alcohol Intake Preferences in Rats
    (Wiley, 2025-03)
    Macarena Díaz‐Ubilla
    ;
    Aliosha I. Figueroa‐Valdés
    ;
    Hugo E. Tobar
    ;
    María Elena Quintanilla
    ;
    Eugenio Díaz
    <jats:title>ABSTRACT</jats:title><jats:p>Growing preclinical and clinical evidence suggests a link between gut microbiota dysbiosis and problematic alcohol consumption. Extracellular vesicles (EVs) are key mediators involved in bacteria‐to‐host communication. However, their potential role in mediating addictive behaviour remains unexplored. This study investigates the role of gut microbiota‐derived bacterial extracellular vesicles (bEVs) in driving high alcohol consumption. bEVs were isolated from the gut microbiota of a high alcohol‐drinking rat strain (UChB rats), either ethanol‐naïve or following chronic alcohol consumption and administered intraperitoneally or orally to alcohol‐rejecting male and female Wistar rats. Both types of UChB‐derived bEVs increased Wistar's voluntary alcohol consumption (three bottle choice test) up to 10‐fold (<jats:italic>p</jats:italic> &lt; 0.0001), indicating that bEVs are able and sufficient to transmit drinking behaviour across different rat strains. Molecular analysis revealed that bEVs administration did not induce systemic or brain inflammation in the recipient animals, suggesting that the increased alcohol intake triggered by UChB‐derived bEVs operates through an inflammation‐independent mechanism. Furthermore, we demonstrate that the vagus nerve mediates the bEV‐induced increase in alcohol consumption, as bilateral vagotomy completely abolished the high drinking behaviour induced by both intraperitoneally injected and orally administered bEVs. Thus, this study identifies bEVs as a novel mechanism underlying gut microbiota‐induced high alcohol intake in a vagus nerve‐dependent manner.</jats:p>
      7
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      4
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    Scopus© Citations 2  2
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    Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use
    (2023)
    María Elena Quintanilla
    ;
    Paola Morales
    ;
    Daniela Santapau
    ;
    Alba Ávila
    ;
    Carolina Ponce
    <jats:p>Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal–striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.</jats:p>
      7Scopus© Citations 6
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    Alcohol’s harm to others: An international collaborative project
    (2016)
    Sarah Callinan
    ;
    Anne-Marie Laslett
    ;
    Dag Rekve
    ;
    Robin Room
    ;
    Orratai Waleewong
    <jats:p>Callinan, S., Laslett, A., Rekve, D., Room, R., Waleewong, O., Benegal, V., Casswell, S., Florenzano, R., Hanh, H., Hanh, V., Hettige, S., Huckle, T., Ibanga, A., Obot, I., Rao, G., Siengsounthone, L., Rankin, G., &amp; Thamarangsi, T. (2016). Alcohol’s harm to others: An international collaborative project. The International Journal Of Alcohol And Drug Research, 5(2), 25-32. doi:http://dx.doi.org/10.7895/ijadr.v5i2.218Aims: This paper outlines the methods of a collaborative population survey project measuring the range and magnitude of alcohol’s harm to others internationally.Setting: Seven countries participating in the World Health Organization (WHO) and ThaiHealth Promotion Foundation (ThaiHealth) research project titled “The Harm to Others from Drinking,” along with two other countries with similar studies, will form the core of a database which will incorporate data from other countries in the future.Measures: The WHO-ThaiHealth research project developed two comparable versions of a survey instrument, both measuring harm from others’ drinking to the respondent and the respondent’s children.Design: Surveys were administered via face-to-face methods in seven countries, while similar surveys were administered via computer-assisted telephone interviews in two additional countries. Responses from all surveys will be compiled in an international database for the purpose of international comparisons.Discussion: Harms from the alcohol consumption of others are intertwined with the cultural norms where consumption occurs. The development of this database will make it possible to look beyond reports and analyses at national levels, and illuminate the relationships between consumption, harms, and culture.Conclusions: This database will facilitate work describing the prevalence, patterning, and predictors of personal reports of harm from others’ drinking cross-nationally.</jats:p>
      2
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    Scoping Response System Management of Alcohol's Harm to others in Lower Middle Income Countries
    (2016)
    Anne-Marie Louise Laslett
    ;
    Orratai Waleewong
    ;
    Isidore Obot
    ;
    Vivek Benegal
    ;
    Siri Hettige
    <jats:sec><jats:title>Aims</jats:title><jats:p> As part of the WHO Harm from others' drinking project, Thailand, Sri Lanka, India, Chile, Nigeria and Vietnam undertook scoping studies to examine: which service agencies in low and middle income countries responded to people affected by others' drinking; how commonly key informants from these agencies indicated alcohol was part of the problems they managed; and whether any routine reporting systems collected information on alcohol's harm to others (AHTO) and the types and examples of harms experienced across the six countries. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Researchers synthetised within country peer-review literature, reports, news and agency website information. Additionally, researchers interviewed key informants to investigate current structures, functions and practices of service agencies, and in particular their recording practices surrounding cases involving others' drinking. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 111 key informants agreed to participate from 91 purposively selected agencies from health, social protection, justice and police, and ‘other' sectors. National and provincial level data, as well as state-run and civil society agency data were collected. Diverse service response systems managed AHTO in the different countries. A large range in the percentage of all cases attributed to AHTO was identified. Case story examples from each country illustrate the different responses to, and the nature of, many severe problems experienced because of others' drinking. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> AHTO was a major issue for service systems in LMIC, and significantly contributed to their workload, yet, very few recording systems routinely collected AHTO data. Recommendations are outlined to improve AHTO data collection across multiple sectors and enable LMIC to better identify and respond to AHTO. </jats:p></jats:sec>
    Scopus© Citations 12  1
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    Innate gut microbiota predisposes to high alcohol consumption
    (2021)
    EZQUER, EDUARDO FERNANDO  
    ;
    Maria Elena Quintanilla
    ;
    Francisco Moya‐Flores
    ;
    Paola Morales
    ;
    MUNITA SEPULVEDA, JOSE MANUEL  
    Scopus© Citations 34  5
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    Scopus© Citations 34  2
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      3
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    Scopus© Citations 22  2