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A Novel Morphine Drinking Model of Opioid Dependence in Rats

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...

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Autores principales: Berríos-Cárcamo, Pablo, Quezada, Mauricio, Santapau, Daniela, Morales, Paola, Olivares, Belén, Ponce, Carolina, Ávila, Alba, De Gregorio, Cristian, Ezquer, Marcelo, Quintanilla, María Elena, Herrera-Marschitz, Mario, Israel, Yedy, Ezquer, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999131/
https://www.ncbi.nlm.nih.gov/pubmed/35409269
http://dx.doi.org/10.3390/ijms23073874
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author Berríos-Cárcamo, Pablo
Quezada, Mauricio
Santapau, Daniela
Morales, Paola
Olivares, Belén
Ponce, Carolina
Ávila, Alba
De Gregorio, Cristian
Ezquer, Marcelo
Quintanilla, María Elena
Herrera-Marschitz, Mario
Israel, Yedy
Ezquer, Fernando
author_facet Berríos-Cárcamo, Pablo
Quezada, Mauricio
Santapau, Daniela
Morales, Paola
Olivares, Belén
Ponce, Carolina
Ávila, Alba
De Gregorio, Cristian
Ezquer, Marcelo
Quintanilla, María Elena
Herrera-Marschitz, Mario
Israel, Yedy
Ezquer, Fernando
author_sort Berríos-Cárcamo, Pablo
collection PubMed
description 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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spelling pubmed-89991312022-04-12 A Novel Morphine Drinking Model of Opioid Dependence in Rats Berríos-Cárcamo, Pablo Quezada, Mauricio Santapau, Daniela Morales, Paola Olivares, Belén Ponce, Carolina Ávila, Alba De Gregorio, Cristian Ezquer, Marcelo Quintanilla, María Elena Herrera-Marschitz, Mario Israel, Yedy Ezquer, Fernando Int J Mol Sci Article 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. MDPI 2022-03-31 /pmc/articles/PMC8999131/ /pubmed/35409269 http://dx.doi.org/10.3390/ijms23073874 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Berríos-Cárcamo, Pablo
Quezada, Mauricio
Santapau, Daniela
Morales, Paola
Olivares, Belén
Ponce, Carolina
Ávila, Alba
De Gregorio, Cristian
Ezquer, Marcelo
Quintanilla, María Elena
Herrera-Marschitz, Mario
Israel, Yedy
Ezquer, Fernando
A Novel Morphine Drinking Model of Opioid Dependence in Rats
title A Novel Morphine Drinking Model of Opioid Dependence in Rats
title_full A Novel Morphine Drinking Model of Opioid Dependence in Rats
title_fullStr A Novel Morphine Drinking Model of Opioid Dependence in Rats
title_full_unstemmed A Novel Morphine Drinking Model of Opioid Dependence in Rats
title_short A Novel Morphine Drinking Model of Opioid Dependence in Rats
title_sort novel morphine drinking model of opioid dependence in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999131/
https://www.ncbi.nlm.nih.gov/pubmed/35409269
http://dx.doi.org/10.3390/ijms23073874
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