A Novel Morphine Drinking Model of Opioid Dependence in Rats

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dc.contributor.authorBerríos, Pablo
dc.contributor.authorQuezada, Mauricio
dc.contributor.authorSantapau, Daniela
dc.contributor.authorMorales, Paola
dc.contributor.authorOlivares, Belén
dc.contributor.authorPonce, Carolina
dc.contributor.authorÁvila, Alba
dc.contributor.authorDe Gregorio, Cristian
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorQuintanilla, María
dc.contributor.authorHerrera, Mario
dc.contributor.authorIsrael, Yedy
dc.contributor.authorEzquer, Fernando
dc.date.accessioned2022-11-14T20:02:10Z
dc.date.available2022-11-14T20:02:10Z
dc.date.issued2022
dc.description.abstractAbstract: 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.es
dc.description.versionVersión publicadaes
dc.identifier.citationBerríos-Cárcamo, P.; Quezada, M.; Santapau, D.; Morales, P.; Olivares, B.; Ponce, C.; Ávila, A.; De Gregorio, C.; Ezquer, M.; Quintanilla, M.E.; et al. A Novel Morphine Drinking Model of Opioid Dependence in Rats. Int. J. Mol. Sci. 2022, 23, 3874. https://doi.org/ 10.3390/ijms23073874es
dc.identifier.urihttps://doi.org/10.3390/ijms23073874es
dc.identifier.urihttp://hdl.handle.net/11447/6661
dc.language.isoenes
dc.subjectMorphinees
dc.subjectOpioidses
dc.subjectAddictiones
dc.subjectOral intakees
dc.subjectAnimal modeles
dc.subjectDependencees
dc.subjectQuininees
dc.titleA Novel Morphine Drinking Model of Opioid Dependence in Ratses
dc.typeArticlees
dcterms.sourceInternational Journal of Molecular Scienceses

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