Long-Evans rats acquire operant self-administration of 20% ethanol without sucrose fading.
Long-Evans rats acquire operant self-administration of 20% ethanol without sucrose fading.
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DOI：
10.1038/npp.2010.15
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发表时间：
2010-06
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开发用于治疗酒精使用障碍（AUDs）的新药的主要障碍是缺乏引起高消耗的临床前口服乙醇消耗范例。我们之前已经证明，在两瓶选择范例中间歇暴露于20%乙醇的大鼠将消耗比连续接触而不使用缺水或蔗糖褪色的大鼠多两倍的乙醇（5-6 g/kg/24小时）。vs. 2-3 g/kg/24 hr）。在这项研究中，我们已经适应了操作性自我管理模式的模型。Long-Evans大鼠在两个时间表之一中过夜获得20%乙醇：1.间歇性（星期一、星期三和星期五）或2.）每天（周一至周五）。随着过夜阶段的进展，两组均显示出饮酒量（3-6 g/kg/14 hr）的稳定增加，而不使用蔗糖褪色程序。在采集阶段后，20%乙醇组消耗的乙醇显著多于训练消耗10%乙醇的动物（1.5 g/kg/30 min vs. 0.7 g/kg/30 min），并达到显著更高的血液乙醇浓度。此外，训练史（20%乙醇与10%乙醇，蔗糖褪色）对随后的自我施用较高浓度的乙醇有显著影响。管理的药理应激育亨宾后灭绝引起了显着恢复乙醇寻求行为。这两种20%乙醇模型都显示出希望，并适合研究的维护，动机和恢复。此外，训练动物在不使用蔗糖褪色的情况下对乙醇进行杠杆按压，消除了自我给药研究中的潜在混淆。
A major obstacle in the development of new medications for the treatment of alcohol use disorders (AUDs) has been the lack of preclinical, oral ethanol consumption paradigms that elicit high consumption. We have previously shown that rats exposed to 20% ethanol intermittently in a two-bottle choice paradigm will consume two times more ethanol than those given continuous access without the use of water deprivation or sucrose fading (5–6 g/kg/24hr. vs. 2–3 g/kg/24hr, respectively). In this study, we have adapted the model to an operant self-administration paradigm. Long-Evans rats were given access to 20% ethanol in overnight sessions on one of two schedules: 1.) intermittent (Monday, Wednesday, and Friday) or 2.) daily (Monday through Friday). With the progression of the overnight sessions, both groups showed a steady escalation in drinking (3–6 g/kg/14hr) without the use of a sucrose fading procedure. Following the acquisition phase, the 20% ethanol groups consumed significantly more ethanol than animals trained to consume 10% ethanol with a sucrose fade (1.5 g/kg/30min vs. 0.7 g/kg/30min) and reached significantly higher blood ethanol concentrations. Additionally, training history (20% ethanol vs. 10% ethanol with sucrose fade) had a significant effect on the subsequent self-administration of higher concentrations of ethanol. Administration of the pharmacological stressor yohimbine following extinction caused a significant reinstatement of ethanol-seeking behavior. Both 20% ethanol models show promise and are amenable to the study of maintenance, motivation, and reinstatement. Furthermore, training animals to lever press for ethanol without the use of sucrose fading removes a potential confound from self-administration studies.
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影响因子：
2.3
作者：
Czachowski, CL;Santini, LA;Samson, HH
通讯作者：
Samson, HH
DOI：
10.1111/j.1530-0277.2008.00678.x
发表时间：
2008-09-01
影响因子：
3.2
作者：
Gilpin, N. W.;Richardson, H. N.;Koob, G. F.
通讯作者：
Koob, G. F.
影响因子：
3.3
作者：
Funk, D;Li, Z;Lê, AD
通讯作者：
Lê, AD
影响因子：
7.6
作者：
Heyser, CJ;Schulteis, G;Koob, GF
通讯作者：
Koob, GF
影响因子：
3.4
作者：
Hölter, SM;Henniger, MSH;Spanagel, R
通讯作者：
Spanagel, R