Fentanyl vapor self-administration model in mice to study opioid addiction.
Fentanyl vapor self-administration model in mice to study opioid addiction.
复制标题
小鼠芬太尼蒸气自我给药模型研究阿片类药物成瘾。
DOI：
10.1126/sciadv.abc0413
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发表时间：
2020
期刊：
影响因子：
13.6
通讯作者：
Vendruscolo,LF
中科院分区：
文献类型：
--
作者：
Moussawi,K;Ortiz,MM;Gantz,SC;Tunstall,BJ;Marchette,RCN;Bonci,A;Koob,GF;Vendruscolo,LF
静脉给药被认为是研究啮齿动物药物成瘾神经生物学的“金标准”模型。然而，它在小鼠中的使用受到静脉导管插入术频繁并发症的限制。鉴于在生物医学研究中使用小鼠的许多优点，我们开发了一种使用蒸发芬太尼的阿片类药物自我给药的非侵入性小鼠模型。小鼠容易自我施用芬太尼蒸汽，滴定其药物摄入量，并表现出成瘾样行为，包括药物摄入量的增加，戒断的躯体体征，尽管受到惩罚但仍摄入药物，以及恢复药物寻求。腹侧被盖区多巴胺神经元的电生理记录显示，在芬太尼蒸汽自我给药的长期戒断期间，GABA受体依赖性电流的振幅较低。这种芬太尼自我给药的小鼠模型概括了阿片类药物成瘾的关键特征，克服了静脉内模型的局限性，并允许以前所未有的方式研究阿片类药物成瘾的神经生物学。
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 GABABreceptor–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.