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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

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dc.contributor.authorEzquer, Fernando
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorGallardo, Javiera
dc.contributor.authorQuintanilla, María
dc.contributor.authorMorales, Paola
dc.contributor.authorSantapau, Daniela
dc.contributor.authorÁvila, Alba
dc.contributor.authorPonce, Carolina
dc.contributor.authorBerrios, Pablo
dc.contributor.authorOlivares, Belén
dc.contributor.authorHerrera, Mario
dc.contributor.authorIsrael, Yedy
dc.date.accessioned2024-03-20T13:14:45Z
dc.date.available2024-03-20T13:14:45Z
dc.date.issued2023
dc.description.abstractChronic 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.
dc.description.versionPublicada
dc.identifier.citationQuintanilla, M.E.; Morales, P.; Santapau, D.; Ávila, A.; Ponce, C.; Berrios-Cárcamo, P.; Olivares, B.; Gallardo, J.; Ezquer, M.; Herrera-Marschitz, M.; et al. Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use. Int. J. Mol. Sci. 2023, 24, 17081. https://doi.org/10.3390/ ijms242317081
dc.identifier.doihttps://doi.org/10.3390/ijms242317081
dc.identifier.urihttps://hdl.handle.net/11447/8552
dc.language.isoen
dc.subjectAnimal model
dc.subjectNeurodegeneration
dc.subjectOpioid addiction
dc.subjectBrain damage
dc.subjectNeuroinflammation
dc.subjectPolydrug
dc.subjectDependence
dc.titleChronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceInternational journal of molecular sciences
dspace.entity.typePublication
relation.isAuthorOfPublicationc74766c7-dad8-4d11-b35d-01da0664f3da
relation.isAuthorOfPublication9cd4a8e6-6ba1-4344-80a2-45c260864d4c
relation.isAuthorOfPublication.latestForDiscovery9cd4a8e6-6ba1-4344-80a2-45c260864d4c

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