Oral oxycodone self-administration leads to features of opioid misuse in male and female mice.
Addict Biol
; 28(1): e13253, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36577735
ABSTRACT
Use of prescription opioids, particularly oxycodone, is an initiating factor driving the current opioid epidemic. There are several challenges with modelling oxycodone abuse. First, prescription opioids including oxycodone are orally self-administered and have different pharmacokinetics and dynamics than morphine or fentanyl, which have been more commonly used in rodent research. This oral route of administration determines the pharmacokinetic profile, which then influences the establishment of drug-reinforcement associations in animals. Moreover, the pattern of intake and the environment in which addictive drugs are self-administered are critical determinants of the levels of drug intake, of behavioural sensitization and of propensity to relapse behaviour. These are all important considerations when modelling prescription opioid use, which is characterized by continuous drug access in familiar environments. Thus, to model features of prescription opioid use and the transition to abuse, we designed an oral, homecage-based oxycodone self-administration paradigm. Mice voluntarily self-administer oxycodone in this paradigm without any taste modification such as sweeteners, and the majority exhibit preference for oxycodone, escalation of intake, physical signs of dependence and reinstatement of seeking after withdrawal. In addition, a subset of animals demonstrate drug taking that is resistant to aversive consequences. This model is therefore translationally relevant and useful for studying the neurobiological substrates of prescription opioid abuse.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxicodona
/
Transtornos Relacionados ao Uso de Opioides
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Addict Biol
Assunto da revista:
TRANSTORNOS RELACIONADOS COM SUBSTANCIAS
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos