Repositorio
Institucional

Ezquer, Fernando

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

A Novel Morphine Drinking Model of Opioid Dependence in Rats

MDPI

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

en

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.

artículo original

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.

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.

10.3390/ijms23073874

PDF

morphine

opioids

addiction

oral intake

animal model

dependence

quinine

MAINTENANCE

PREFERENCE

GENDER

MICE

WITHDRAWAL

RECEPTORS

SCHEDULE

BEHAVIOR

ACCESS

Bioquímica y Biología Molecular

Química

Multidisciplinar

morfina

opioides

adicción

ingesta oral

modelo animal

dependencia

quinina

MANTENIMIENTO

PREFERENCIA

GÉNERO

RATONES

RETIRADA

RECEPTORES

HORARIO

COMPORTAMIENTO

ACCESO

Abuso de Substancias

Farmacología y Farmacia

Neurociencias

A Novel Morphine Drinking Model of Opioid Dependence in Rats

artículo original

version publicada

CC BY 4.0

CC BY 4.0

acceso abierto

acceso abierto

ANID-FONDECYT 1200287

ANID-FONDECYT 3210276

ANID ACT210012

ANID FONDECYT 1200287

ANID FONDECYT 3210276

WOS:000781981000001