Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2023
Author(s)
María Elena Quintanilla
Paola Morales
Daniela Santapau
Alba Ávila
Carolina Ponce
Mario Herrera-Marschitz
Javiera Gallardo
Yedy Israel
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal–striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.</jats:p>
Cite this document
Quintanilla, M. E., Morales, P., Santapau, D., Ávila, A., Ponce, C., Berrios-Cárcamo, P., Olivares, B., Gallardo, J., Ezquer, M., Herrera-Marschitz, M., Israel, Y., & Ezquer, F. (2023). Chronic voluntary morphine intake is associated with changes in brain structures involved in drug dependence in a rat model of polydrug use. International Journal of Molecular Sciences, 24(23), 17081. https://doi.org/10.3390/ijms242317081
Project(s)
Subjects
animal model
;
brain damage
;
dependence
;
neurodegeneration
;
neuroinflammation
;
opioid addiction
;
polydrug
;
analgesics, opioid
;
animals
;
brain
;
ethanol
;
humans
;
morphine
;
morphine dependence
;
naloxone
;
narcotic antagonists
;
rats
;
rats, wistar
;
substance-related disorders
;
alcohol
;
dopamine transporter
;
interleukin 1beta
;
interleukin 6
;
malonaldehyde
;
messenger rna
;
morphine
;
morphine sulfate
;
myelin basic protein
;
naloxone
;
nicotine
;
proteolipid protein
;
tumor necrosis factor
;
vesicular glutamate transporter 1
;
alcohol
;
morphine
;
naloxone
;
narcotic analgesic agent
;
narcotic antagonist
;
alcoholism
;
animal experiment
;
animal model
;
animal tissue
;
article
;
brain damage
;
chronic drug administration
;
controlled study
;
corpus striatum
;
demyelination
;
drug dependence
;
female
;
glia
;
male
;
morphine addiction
;
multiple drug abuse
;
nerve fiber degeneration
;
nervous system inflammation
;
neurofilament
;
nonhuman
;
nucleus accumbens
;
opiate addiction
;
oxidative stress
;
prefrontal cortex
;
rat
;
tobacco dependence
;
withdrawal syndrome
;
animal
;
brain
;
drug dependence
;
human
;
morphine addiction
;
wistar rat