A Novel Morphine Drinking Model of Opioid Dependence in Rats
| Primer Autor |
Ezquer, Fernando
|
| Co-autores |
Berrios-Carcamo, Pablo
Quezada, Mauricio
Santapau, Daniela
Morales, Paola
Olivares, Belen
Ponce, Carolina
avila, Alba
De Gregorio, Cristian
Ezquer, Marcelo
Quintanilla, Maria Elena
Herrera-Marschitz, Mario
Israel, Yedy
|
| Título |
A Novel Morphine Drinking Model of Opioid Dependence in Rats
|
| Editorial |
MDPI
|
| Revista |
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
|
| Lenguaje |
en
|
| Resumen |
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.
|
| Tipo de Recurso |
artículo original
|
| Description |
The technical assistance of Camila Ezquer, Jorge Ruiz, and Catalina Vallejos is greatly appreciated., This work was supported by FONDECYT 1200287 and ANID ACT210012 to Fernando Ezquer and FONDECYT 3210276 to Pablo Berrios-Carcamo.
Se agradece mucho la asistencia técnica de Camila Ezquer, Jorge Ruiz y Catalina Vallejos., Este trabajo fue apoyado por FONDECYT 1200287 y ANID ACT210012 a Fernando Ezquer y FONDECYT 3210276 a Pablo Berrios-Carcamo.
|
| doi |
10.3390/ijms23073874
|
| Formato Recurso |
PDF
|
| Palabras Claves |
morphine
opioids
addiction
oral intake
animal model
dependence
quinine
MAINTENANCE
PREFERENCE
GENDER
MICE
WITHDRAWAL
RECEPTORS
SCHEDULE
BEHAVIOR
ACCESS
|
| Ubicación del archivo | |
| Categoría OCDE |
Bioquímica y Biología Molecular
Química
Multidisciplinar
|
| Materias |
morfina
opioides
adicción
ingesta oral
modelo animal
dependencia
quinina
MANTENIMIENTO
PREFERENCIA
GÉNERO
RATONES
RETIRADA
RECEPTORES
HORARIO
COMPORTAMIENTO
ACCESO
|
| Título de la cita (Recomendado-único) |
A Novel Morphine Drinking Model of Opioid Dependence in Rats
|
| Identificador del recurso (Mandatado-único) |
artículo original
|
| Versión del recurso (Recomendado-único) |
version publicada
|
| License |
CC BY 4.0
|
| Condición de la licencia (Recomendado-repetible) |
CC BY 4.0
|
| Derechos de acceso |
acceso abierto
|
| Access Rights |
acceso abierto
|
| Referencia del Financiador (Mandatado si es aplicable-repetible) |
ANID-FONDECYT 1200287
ANID-FONDECYT 3210276
ANID ACT210012
ANID FONDECYT 1200287
ANID FONDECYT 3210276
|
| Id de Web of Science |
WOS:000781981000001
|
cienciaabierta.ufro.cl
ciencia.abierta@ufrontera.cl