Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkers
Rodent models are useful for understanding the mechanisms that underlie opioid addiction, but most preclinical studies have focused on rewarding and consummatory aspects of opioids without components of dependence-induced escalation of drug taking or seeking. We characterized several opioid-related...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2023-03-01
|
Series: | Addiction Neuroscience |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2772392522000529 |
_version_ | 1811166141655023616 |
---|---|
author | Renata C.N. Marchette Erika R. Carlson Nadia Said George F. Koob Leandro F. Vendruscolo |
author_facet | Renata C.N. Marchette Erika R. Carlson Nadia Said George F. Koob Leandro F. Vendruscolo |
author_sort | Renata C.N. Marchette |
collection | DOAJ |
description | Rodent models are useful for understanding the mechanisms that underlie opioid addiction, but most preclinical studies have focused on rewarding and consummatory aspects of opioids without components of dependence-induced escalation of drug taking or seeking. We characterized several opioid-related behaviors in mice using a model of vaporized fentanyl self-administration. Male and female C57BL/6J mice were assigned to short-access (ShA; 1 h, nondependent) or long-access (LgA; 6 h, dependent) fentanyl vapor self-administration and subsequently tested in a battery of behavioral tests, followed by blood collection during withdrawal. Compared with mice in the ShA group, mice in the LgA group escalated their fentanyl intake, were more motivated to work to obtain the drug, exhibited greater hyperalgesia, and exhibited greater signs of naloxone-precipitated withdrawal. Principal component analysis indicated the emergence of two independent behavioral constructs: “intake/motivation” and “hyperalgesia/punished seeking.” In mice in the LgA condition only, “hyperalgesia/punished seeking” was associated with plasma levels of proinflammatory interleukin-17 (IL-17), chemokine (C-C motif) ligand 4 (CCL-4), and tumor necrosis factor α (TNF-α). Overall, the results suggest that extended access to opioids leads to addiction-like behavior, and some constructs that are associated with addiction-like behavior may be associated with levels of the proinflammatory cytokines/chemokines IL-17, TNF-α, and CCL-4 in blood. |
first_indexed | 2024-04-10T15:47:44Z |
format | Article |
id | doaj.art-b213fa7d64a345e39ea41f6d751be200 |
institution | Directory Open Access Journal |
issn | 2772-3925 |
language | English |
last_indexed | 2024-04-10T15:47:44Z |
publishDate | 2023-03-01 |
publisher | Elsevier |
record_format | Article |
series | Addiction Neuroscience |
spelling | doaj.art-b213fa7d64a345e39ea41f6d751be2002023-02-12T04:15:49ZengElsevierAddiction Neuroscience2772-39252023-03-015100057Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkersRenata C.N. Marchette0Erika R. Carlson1Nadia Said2George F. Koob3Leandro F. Vendruscolo4Neurobiology of Addiction Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, BRC 08A505.16, Baltimore, MD 21224, USA; Corresponding author.Neurobiology of Addiction Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, BRC 08A505.16, Baltimore, MD 21224, USANeurobiology of Addiction Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, BRC 08A505.16, Baltimore, MD 21224, USANeurobiology of Addiction Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, BRC 08A505.16, Baltimore, MD 21224, USAStress & Addiction Neuroscience Unit, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism Intramural Research Programs, National Institutes of Health, Baltimore, MD, USARodent models are useful for understanding the mechanisms that underlie opioid addiction, but most preclinical studies have focused on rewarding and consummatory aspects of opioids without components of dependence-induced escalation of drug taking or seeking. We characterized several opioid-related behaviors in mice using a model of vaporized fentanyl self-administration. Male and female C57BL/6J mice were assigned to short-access (ShA; 1 h, nondependent) or long-access (LgA; 6 h, dependent) fentanyl vapor self-administration and subsequently tested in a battery of behavioral tests, followed by blood collection during withdrawal. Compared with mice in the ShA group, mice in the LgA group escalated their fentanyl intake, were more motivated to work to obtain the drug, exhibited greater hyperalgesia, and exhibited greater signs of naloxone-precipitated withdrawal. Principal component analysis indicated the emergence of two independent behavioral constructs: “intake/motivation” and “hyperalgesia/punished seeking.” In mice in the LgA condition only, “hyperalgesia/punished seeking” was associated with plasma levels of proinflammatory interleukin-17 (IL-17), chemokine (C-C motif) ligand 4 (CCL-4), and tumor necrosis factor α (TNF-α). Overall, the results suggest that extended access to opioids leads to addiction-like behavior, and some constructs that are associated with addiction-like behavior may be associated with levels of the proinflammatory cytokines/chemokines IL-17, TNF-α, and CCL-4 in blood.http://www.sciencedirect.com/science/article/pii/S2772392522000529Substance use disorder (SUD)Opioid use disorder (OUD)HyperalgesiaExtended accessAddiction-like behaviorOperant self-administration |
spellingShingle | Renata C.N. Marchette Erika R. Carlson Nadia Said George F. Koob Leandro F. Vendruscolo Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkers Addiction Neuroscience Substance use disorder (SUD) Opioid use disorder (OUD) Hyperalgesia Extended access Addiction-like behavior Operant self-administration |
title | Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkers |
title_full | Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkers |
title_fullStr | Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkers |
title_full_unstemmed | Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkers |
title_short | Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkers |
title_sort | extended access to fentanyl vapor self administration leads to addiction like behaviors in mice blood chemokine cytokine levels as potential biomarkers |
topic | Substance use disorder (SUD) Opioid use disorder (OUD) Hyperalgesia Extended access Addiction-like behavior Operant self-administration |
url | http://www.sciencedirect.com/science/article/pii/S2772392522000529 |
work_keys_str_mv | AT renatacnmarchette extendedaccesstofentanylvaporselfadministrationleadstoaddictionlikebehaviorsinmicebloodchemokinecytokinelevelsaspotentialbiomarkers AT erikarcarlson extendedaccesstofentanylvaporselfadministrationleadstoaddictionlikebehaviorsinmicebloodchemokinecytokinelevelsaspotentialbiomarkers AT nadiasaid extendedaccesstofentanylvaporselfadministrationleadstoaddictionlikebehaviorsinmicebloodchemokinecytokinelevelsaspotentialbiomarkers AT georgefkoob extendedaccesstofentanylvaporselfadministrationleadstoaddictionlikebehaviorsinmicebloodchemokinecytokinelevelsaspotentialbiomarkers AT leandrofvendruscolo extendedaccesstofentanylvaporselfadministrationleadstoaddictionlikebehaviorsinmicebloodchemokinecytokinelevelsaspotentialbiomarkers |