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Fentanyl vapor self-administration model in mice to study opioid addiction

Graphical AbstractHot Off the Press – August 27 , 2020.

This paper describes a new non-invasive model of opioid addiction in mice that is based on fentanyl vapor self-administration. This model allows the study of limited and prolonged drug intake, abstinence, and relapse to drug seeking. Compared to current intravenous models, the new model is more conducive for longer access to drugs and has very low attrition rate. This model enables the investigation of the neurobiology of opioid addiction in unprecedented ways.

Publication Information

Moussawi, K; Ortiz, M M; Gantz, S C; Tunstall, B J; Marchette, R C N; Bonci, A; Koob, G F; Vendruscolo, L F

Fentanyl vapor self-administration model in mice to study opioid addiction. Journal Article

In: Sci Adv, vol. 6, no. 32, pp. eabc0413, 2020.

Abstract | Links

@article{Moussawi:2020aa,
title = {Fentanyl vapor self-administration model in mice to study opioid addiction.},
author = {K Moussawi and M M Ortiz and S C Gantz and B J Tunstall and R C N Marchette and A Bonci and G F Koob and L F Vendruscolo},
url = {https://pubmed.ncbi.nlm.nih.gov/32821843/},
doi = {10.1126/sciadv.abc0413},
year = {2020},
date = {2020-08-01},
urldate = {2020-08-01},
journal = {Sci Adv},
volume = {6},
number = {32},
pages = {eabc0413},
abstract = {Intravenous drug self-administration is considered the "gold standard" model to investigate the neurobiology of drug addiction in rodents. However, its use in mice is limited by frequent complications of intravenous catheterization. Given the many advantages of using mice in biomedical research, we developed a noninvasive mouse model of opioid self-administration using vaporized fentanyl. Mice readily self-administered fentanyl vapor, titrated their drug intake, and exhibited addiction-like behaviors, including escalation of drug intake, somatic signs of withdrawal, drug intake despite punishment, and reinstatement of drug seeking. Electrophysiological recordings from ventral tegmental area dopamine neurons showed a lower amplitude of GABA(B) receptor-dependent currents during protracted abstinence from fentanyl vapor self-administration. This mouse model of fentanyl self-administration recapitulates key features of opioid addiction, overcomes limitations of the intravenous model, and allows investigation of the neurobiology of opioid addiction in unprecedented ways.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Intravenous drug self-administration is considered the "gold standard" model to investigate the neurobiology of drug addiction in rodents. However, its use in mice is limited by frequent complications of intravenous catheterization. Given the many advantages of using mice in biomedical research, we developed a noninvasive mouse model of opioid self-administration using vaporized fentanyl. Mice readily self-administered fentanyl vapor, titrated their drug intake, and exhibited addiction-like behaviors, including escalation of drug intake, somatic signs of withdrawal, drug intake despite punishment, and reinstatement of drug seeking. Electrophysiological recordings from ventral tegmental area dopamine neurons showed a lower amplitude of GABA(B) receptor-dependent currents during protracted abstinence from fentanyl vapor self-administration. This mouse model of fentanyl self-administration recapitulates key features of opioid addiction, overcomes limitations of the intravenous model, and allows investigation of the neurobiology of opioid addiction in unprecedented ways.

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  • https://pubmed.ncbi.nlm.nih.gov/32821843/
  • doi:10.1126/sciadv.abc0413

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