Demand for fentanyl becomes inelastic following extended access to fentanyl vapor self-administration.
Demand for fentanyl becomes inelastic following extended access to fentanyl vapor self-administration.
复制标题
在扩展获得芬太尼蒸气自我管理后，对芬太尼的需求变得无弹性。
DOI：
10.1016/j.neuropharm.2020.108355
复制
发表时间：
2021-01
影响因子：
4.7
通讯作者：
Tunstall BJ
中科院分区：
文献类型：
--
作者：
McConnell SA;Brandner AJ;Blank BA;Kearns DN;Koob GF;Vendruscolo LF;Tunstall BJ
阿片类药物使用障碍在美国和世界各国造成了巨大的社会危害。准确捕捉阿片类药物依赖中发生的动机变化的动物模型对于研究这种疾病至关重要。本研究使用阿片类药物蒸汽自我给药模型结合行为经济学方法来确定大鼠是否更有动力“工作”以捍卫其芬太尼的基线摄入量（即，在足够频繁、强烈和长期暴露于自我给药的蒸发芬太尼后，需求更具弹性）。允许雄性大鼠对1.5秒的蒸发的10 mg/ml芬太尼溶液的递送作出反应。在15次短时间（ShA; 1 h）与长时间（LgA; 12 h）自我给药后，我们进行了一个会话间需求曲线程序，并观察到LgA大鼠对芬太尼的非弹性需求（基本值; EV）显著增加，最大反应输出（Omax）增加。在随后的阶段中，单位剂量加倍至3 s芬太尼汽化。在7次ShA与LgA治疗后，我们再次评估了需求，发现LgA大鼠与ShA大鼠相比，除了EV和Omax显著增加外，还表现出显著更高的基线摄入量或“享乐设定点”（Q 0）。这些结果表明，延长获得汽化阿片类药物的自我给药导致行为经济指标的变化，与大鼠成瘾样状态的发展一致。蒸汽模型与相关的行为经济学框架相结合，开辟了新的途径来研究物质使用障碍的失调的动机过程。
Opioid use disorder imposes great societal harm in the United States and in countries worldwide. Animal models that accurately capture motivational changes that occur in opioid dependence are critical to studying this disorder. The present study used a model of opioid vapor self-administration combined with a behavioral economics approach to determine whether rats would be more motivated to “work” to defend their baseline intake of fentanyl (i.e., more inelastic demand) following sufficiently frequent, intense, and chronic exposure to self-administered vaporized fentanyl. Male rats were allowed to respond for deliveries of 1.5-s of vaporized 10 mg/ml fentanyl solution. Following 15 sessions of short access (ShA; 1 h) vs. long access (LgA; 12 h) to self-administration, we conducted a between-sessions demand curve procedure, and observed significantly more inelastic demand for fentanyl (Essential Value; EV), and increased maximal response output (Omax) in LgA compared with ShA rats. In a subsequent phase, the unit-dose was doubled to 3 s of fentanyl vaporization. After seven ShA vs. LgA sessions, we assessed demand again and found that LgA rats, contrasted to ShA rats, demonstrated significantly higher baseline intake or “hedonic setpoint” (Q0), in addition to significantly increased EV and Omax. These results demonstrate that extended access to self-administration of a vaporized opioid causes changes in behavioral economic metrics consistent with development of an addiction-like state in rats. The combination of the vapor model with a translationally relevant behavioral economics framework opens new avenues to study dysregulated motivational processes in substance use disorders.
登录
查看更多内容
影响因子：
3.6
作者：
Christensen, Chesley J.;Silberberg, Alan;Hursh, Steven R.;Roma, Peter G.;Riley, Anthony L.
通讯作者：
Riley, Anthony L.
DOI：
10.1016/j.pbb.2020.173061
发表时间：
2020-12
期刊：
Pharmacology, biochemistry, and behavior
影响因子：
--
作者：
Gutierrez A;Nguyen JD;Creehan KM;Taffe MA
通讯作者：
Taffe MA
影响因子：
3.4
作者：
Kearns DN;Kim JS;Tunstall BJ;Silberberg A
通讯作者：
Silberberg A
影响因子：
3.4
作者：
Jang, Choon-Gon;Whitfield, Timothy;Schulteis, Gery;Koob, George F.;Wee, Sunmee
通讯作者：
Wee, Sunmee
影响因子：
3.4
作者：
Bentzley, Brandon S.;Fender, Kimberly M.;Aston-Jones, Gary
通讯作者：
Aston-Jones, Gary