Cocaine self-administration behaviors in ClockΔ19 mice.
Cocaine self-administration behaviors in ClockΔ19 mice.
复制标题
时钟Δ19小鼠的可卡因自我给药行为。
DOI：
10.1007/s00213-012-2704-2
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发表时间：
2012-09
影响因子：
3.4
通讯作者：
McClung, Colleen A.
中科院分区：
文献类型：
--
作者：
Ozburn, Angela Renee;Larson, Erin Beth;Self, David W.;McClung, Colleen A.
昼夜节律运动输出周期 kaput（时钟）基因在药物奖赏调节中的关键作用已被确定。时钟基因显性失活突变的小鼠（ClockΔ19小鼠）表现出可卡因诱导的条件性位置偏好增加、焦虑和抑郁样行为减少、对颅内自我刺激的敏感性增加以及腹侧被盖区多巴胺能细胞活性增加。我们试图确定这种过度享乐表型是否延伸到可卡因自我给药和动机测量。进行了两个单独的系列测试程序（n=7-10/基因型/时间表）。测试从获取蔗糖颗粒自我给药、植入静脉导管、获取可卡因自我给药和剂量反应测试（固定比率或渐进比率）开始。为了评估采集行为的昼夜变化，这些会话发生在 Zeitgeber 2 (ZT2) 或 ZT14。 WT 和 ClockΔ19 小鼠在 ZT2 和 ZT14 表现出相似的学习能力并且很容易获得食物自我管理。然而，只有 ClockΔ19 小鼠在 ZT2 时获得了可卡因自我给药。更大比例的 ClockΔ19 小鼠在 ZT2 和 ZT14 达到采集标准。 ClockΔ19 小鼠比 WT 小鼠自我施用更多的可卡因。使用强化剂量反应范例的固定比例和渐进比例方案，我们发现可卡因在 ClockΔ19 小鼠中是比 WT 小鼠更有效的强化剂。我们的结果表明，Clock 基因在可卡因强化中发挥着重要作用，而 CLOCK 功能的降低会增加可卡因使用的脆弱性。
A key role has been identified for the circadian locomotor output cycles kaput (Clock) gene in the regulation of drug reward. Mice bearing a dominant negative mutation in the Clock gene (ClockΔ19 mice) exhibit increased cocaine-induced conditioned place preference, reduced anxiety- and depression-like behavior, increased sensitivity to intracranial self-stimulation, and increased do-paminergic cell activity in the ventral tegmental area. We sought to determine if this hyperhedonic phenotype extends to cocaine self-administration and measures of motivation. Two separate serial testing procedures were carried out (n=7–10/genotype/schedule). Testing began with acquisition of sucrose pellet self-administration, implantation of intravenous catheter, acquisition of cocaine self-administration, and dose–response testing (fixed ratio or progressive ratio). To evaluate diurnal variations in acquisition behavior, these sessions occurred at Zeitgeber 2 (ZT2) or ZT14. WT and ClockΔ19 mice exhibited similar learning and readily acquired food self-administration at both ZT2 and ZT14. However, only ClockΔ19 mice acquired cocaine self-administration at ZT2. A greater percentage of ClockΔ19 mice reached acquisition criteria at ZT2 and ZT14. ClockΔ19 mice self-administered more cocaine than WT mice. Using fixed ratio and progressive ratio schedules of reinforcement dose–response paradigms, we found that cocaine is a more efficacious reinforcer in ClockΔ19 mice than in WT mice. Our results demonstrate that the Clock gene plays an important role in cocaine reinforcement and that decreased CLOCK function increases vulnerability for cocaine use.
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影响因子：
4.2
作者：
Kandel, DB;Huang, FY;Davies, M
通讯作者：
Davies, M
影响因子：
3.4
作者：
Caine, SB;Negus, SS;Mello, NK
通讯作者：
Mello, NK
影响因子：
2.9
作者：
Lynch, Wendy J.;Girgenti, Matthew J.;Taylor, Jane R.
通讯作者：
Taylor, Jane R.
DOI：
10.1038/nrg2430
发表时间：
2008-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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影响因子：
16.2
作者：
Hnasko, Thomas S.;Chuhma, Nao;Zhang, Hui;Goh, Germaine Y.;Sulzer, David;Palmiter, Richard D.;Rayport, Stephen;Edwards, Robert H.
通讯作者：
Edwards, Robert H.