A limited access oral oxycodone paradigm produces physical dependence and mesocorticolimbic region-dependent increases in DeltaFosB expression without preference.
Neuropharmacology
; 205: 108925, 2022 03 01.
Article
en En
| MEDLINE
| ID: mdl-34921830
ABSTRACT
The abuse of oral formulations of prescription opioids has precipitated the current opioid epidemic. We developed an oral oxycodone consumption model consisting of a limited access (4 h) two-bottle choice drinking in the dark (TBC-DID) paradigm and quantified dependence with naloxone challenge using mice of both sexes. We also assessed neurobiological correlates of withdrawal and dependence elicited via oral oxycodone consumption using immunohistochemistry for DeltaFosB (ΔFosB), a transcription factor described as a molecular marker for drug addiction. Neither sex developed a preference for the oxycodone bottle, irrespective of oxycodone concentration, bottle position or prior water restriction. Mice that volitionally consumed oxycodone exhibited hyperlocomotion in an open field test and supraspinal but not spinally-mediated antinociception. Both sexes also developed robust, dose-dependent levels of opioid withdrawal that was precipitated by the opioid antagonist naloxone. Oral oxycodone consumption followed by naloxone challenge led to mesocorticolimbic region-dependent increases in the number of ΔFosB expressing cells. Naloxone-precipitated withdrawal jumps, but not the oxycodone bottle % preference, was positively correlated with the number of ΔFosB expressing cells specifically in the nucleus accumbens shell. Thus, limited access oral consumption of oxycodone produced physical dependence and increased ΔFosB expression despite the absence of opioid preference. Our TBC-DID paradigm allows for the study of oral opioid consumption in a simple, high-throughput manner and elucidates the underlying neurobiological substrates that accompany opioid-induced physical dependence.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxicodona
/
Síndrome de Abstinencia a Sustancias
/
Proteínas Proto-Oncogénicas c-fos
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Analgésicos Opioides
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Trastornos Relacionados con Opioides
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Núcleo Accumbens
Tipo de estudio:
Prognostic_studies
Aspecto:
Patient_preference
Límite:
Animals
Idioma:
En
Revista:
Neuropharmacology
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM