A Novel Morphine Drinking Model of Opioid Dependence in Rats
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2022
Author(s)
Mauricio Quezada
Daniela Santapau
Paola Morales
Carolina Ponce
Alba Ávila
María Elena Quintanilla
Mario Herrera-Marschitz
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>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.</jats:p>
Cite this document
Berríos-Cárcamo, P., Quezada, M., Santapau, D., Morales, P., Olivares, B., Ponce, C., Ávila, A., De Gregorio, C., Ezquer, M., Quintanilla, M. E., Herrera-Marschitz, M., Israel, Y., & Ezquer, F. (2022). A novel morphine drinking model of opioid dependence in rats. International Journal of Molecular Sciences, 23(7), 3874. https://doi.org/10.3390/ijms23073874
Project(s)
Subjects
morphine
;
opioids
;
addiction
;
oral intake
;
animal model
;
dependence
;
quinine
;
animals
;
disease models, animal
;
morphine
;
morphine dependence
;
opioid-related disorders
;
quinine
;
rats
;
taste
;
water
;
drinking water
;
morphine
;
naloxone
;
quinine
;
morphine
;
quinine
;
water
;
analgesia
;
animal experiment
;
animal model
;
article
;
bitter taste
;
conditioning
;
controlled study
;
drug self administration
;
experimental hyperactivity
;
male
;
morphine addiction
;
nonhuman
;
opiate addiction
;
oxidative stress
;
rat
;
signal transduction
;
taste preference
;
thigmotaxis
;
animal
;
disease model
;
opiate addiction
;
taste