Universidad del Desarrollo

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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> < 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>
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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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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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Aspirin and N‐acetylcysteine co‐administration markedly inhibit chronic ethanol intake and block relapse binge drinking: Role of neuroinflammation‐oxidative stress self‐perpetuation
(2019)
Yedy Israel
;
María Elena Quintanilla
;
EZQUER, EDUARDO FERNANDO
;
Paola Morales
;
Daniela Santapau
Scopus© Citations 34 2
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A dual mechanism fully blocks ethanol relapse: Role of vagal innervation
(2022)
María Elena Quintanilla
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EZQUER, EDUARDO FERNANDO
;
Paola Morales
;
Daniela Santapau
;
EZQUER, EDUARDO MARCELO
3
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A dual treatment blocks alcohol binge-drinking relapse: Microbiota as a new player
(2022)
EZQUER, EDUARDO FERNANDO
;
María Elena Quintanilla
;
Paola Morales
;
Daniela Santapau
;
MUNITA SEPULVEDA, JOSE MANUEL
Scopus© Citations 22 2
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Activated mesenchymal stem cell administration inhibits chronic alcohol drinking and suppresses relapse-like drinking in high-alcohol drinker rats
(2019)
EZQUER, EDUARDO FERNANDO
;
María Elena Quintanilla
;
Paola Morales
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EZQUER, EDUARDO MARCELO
;
Carolyne Lespay-Rebolledo
1Scopus© Citations 31 2
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Gene and cell therapy on the acquisition and relapse-like binge drinking in a model of alcoholism: translational options
(2019)
Yedy Israel
;
Quintanilla, María Elena
;
Paola Ezquer
;
Mario Morales
;
Eduardo Rivera-Meza
26Scopus© Citations 4
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Intranasal mesenchymal stem cell secretome administration markedly inhibits alcohol and nicotine self-administration and blocks relapse-intake: mechanism and translational options
(2019)
María Elena Quintanilla
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EZQUER, EDUARDO FERNANDO
;
Paola Morales
;
Daniela Santapau
;
BERRIOS CARCAMO, PABLO ANDRES
14Scopus© Citations 28

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