OLIVARES, MARIA BELEN
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OLIVARES, MARIA BELEN
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molivares@udd.cl
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Scopus Author ID
57194227842

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2023 2023 2022 2022 2021 2021 2020 2020 2019 2019 0.0 0.0 0.2 0.2 0.4 0.4 0.6 0.6 0.8 0.8 1.0 1.0

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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 , BERRIOS CARCAMO, PABLO ANDRES , EZQUER, EDUARDO MARCELO , OLIVARES, MARIA BELEN , Mario Herrera‐Marschitz

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N-Acetylcysteine and Acetylsalicylic Acid Inhibit Alcohol Consumption by Different Mechanisms: Combined Protection

2020 , María Elena Quintanilla , EZQUER, EDUARDO FERNANDO , Paola Morales , EZQUER, EDUARDO MARCELO , OLIVARES, MARIA BELEN , Mario Herrera-Marschitz , Daniela Santapau , Yedy Israel

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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 , OLIVARES, MARIA BELEN , Glauben Landskron , Marcela A. Hermoso , EZQUER, EDUARDO MARCELO , Mario Herrera‐Marschitz , Yedy Israel

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A Novel Morphine Drinking Model of Opioid Dependence in Rats

2022 , BERRIOS CARCAMO, PABLO ANDRES , Mauricio Quezada , Daniela Santapau , Paola Morales , OLIVARES, MARIA BELEN , Carolina Ponce , Alba Ávila , María Elena Quintanilla , EZQUER, EDUARDO MARCELO , DE GREGORIO CONCHA, CRISTIAN ALEJANDRO , Mario Herrera-Marschitz , Yedy Israel , EZQUER, EDUARDO FERNANDO

An animal model of voluntary oral morphine consumption would allow for a pre-clinical evaluation of new treatments aimed at reducing opioid intake in humans. However, the main limitation of oral morphine consumption in rodents is its bitter taste, which is strongly aversive. Taste aversion is often overcome by the use of adulterants, such as sweeteners, to conceal morphine taste or bitterants in the alternative bottle to equalize aversion. However, the adulterants’ presence is the cause for consumption choice and, upon removal, the preference for morphine is not preserved. Thus, current animal models are not suitable to study treatments aimed at reducing consumption elicited by morphine itself. Since taste preference is a learned behavior, just-weaned rats were trained to accept a bitter taste, adding the bitterant quinine to their drinking water for one week. The latter was followed by allowing the choice of quinine or morphine (0.15 mg/mL) solutions for two weeks. Then, quinine was removed, and the preference for morphine against water was evaluated. Using this paradigm, we show that rats highly preferred the consumption of morphine over water, reaching a voluntary morphine intake of 15 mg/kg/day. Morphine consumption led to significant analgesia and hyperlocomotion, and to a marked deprivation syndrome following the administration of the opioid antagonist naloxone. Voluntary morphine consumption was also shown to generate brain oxidative stress and neuroinflammation, signs associated with opioid dependence development. We present a robust two-bottle choice animal model of oral morphine self-administration for the evaluation of therapeutic interventions for the treatment of morphine dependence.

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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 , BERRIOS CARCAMO, PABLO ANDRES , OLIVARES, MARIA BELEN , Mario Herrera-Marschitz , EZQUER, EDUARDO MARCELO , Javiera Gallardo , Yedy Israel , EZQUER, EDUARDO FERNANDO

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.

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