Reversal-specific learning impairments after a binge regimen of methamphetamine in rats: possible involvement of striatal dopamine.
Reversal-specific learning impairments after a binge regimen of methamphetamine in rats: possible involvement of striatal dopamine.
复制标题
大鼠暴食甲基苯丙胺后逆转特异性学习障碍：可能涉及纹状体多巴胺。
DOI：
10.1038/npp.2009.155
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发表时间：
2010-01
影响因子：
7.6
通讯作者：
Marshall, John F.
中科院分区：
文献类型：
--
作者：
Izquierdo, Alicia;Belcher, Annabelle M.;Scott, Lori;Cazares, Victor A.;Chen, Jack;O'Dell, Steven J.;Malvaez, Melissa;Wu, Tiffany;Marshall, John F.
关键词：
越来越多的证据表明，长期使用甲基苯丙胺（mAMPH）会导致人类认知功能的长期损害。除了广泛报道的注意力问题外，mAMPH使用者还表现出学习和记忆缺陷，特别是在需要反应控制的任务上。尽管对动物的mAMPH过量给药导致认知缺陷，但很少有研究试图测试mAMPH暴露后动物的行为灵活性。本研究的目的是评估mAMPH是否会在评估大鼠灵活反应的两个任务中产生损伤：基于触摸屏的辨别逆转学习任务和基于人类执行功能标志性测试威斯康星州卡片分类的注意力转移任务（ASST）。我们在一天内用4次注射2 mg/kg mAMPH（或溶剂）的方案治疗雄性Long-Evans大鼠，这种给药方案先前显示会产生物体识别障碍。然后，我们测试了他们（1）治疗前辨别学习后的逆转学习或（2）注意力转移任务（ASST）。早期逆转学习的准确性受损mAMPH治疗的大鼠。MAMPH预处理也选择性地损害逆转性能在ASST测试，离开集移位性能不变。[125 I]RTI-55结合的尸检分析显示，这种mAMPH方案产生的纹状体多巴胺转运蛋白减少较小（10-20%）但显著。总之，这些结果为不断增长的领域提供了新的信息，记录了mAMPH暴露后认知受损，并构成了广泛报道的人类mAMPH滥用导致的决策缺陷的大鼠模型。
A growing body of evidence indicates that protracted use of methamphetamine (mAMPH) causes long-term impairments in cognitive function in humans. Aside from the widely-reported problems with attention, mAMPH users exhibit learning and memory deficits, particularly on tasks requiring response control. Although binge mAMPH administration to animals results in cognitive deficits, few studies have attempted to test behavioral flexibility in animals following mAMPH exposure. The aim of the current study was to evaluate whether mAMPH would produce impairments in two tasks assessing flexible responding in rats: a touchscreen-based discrimination-reversal learning task and an attentional set shift task (ASST) based on a hallmark test of executive function in humans, the Wisconsin Card Sort. We treated male Long-Evans rats with a regimen of four injections of 2 mg/kg mAMPH (or vehicle) within a single day, a dosing regimen previously shown to produce object recognition impairments. We then tested them on (1) reversal learning following pre-treatment discrimination learning or (2) the attentional set shift task (ASST). Early reversal learning accuracy was impaired in mAMPH-treated rats. MAMPH pretreatment also selectively impaired reversal performance during ASST testing, leaving set-shifting performance intact. Postmortem analysis of [125I]RTI-55 binding revealed small (10–20%) but significant reductions in striatal dopamine transporters produced by this mAMPH regimen. Together, these results lend new information to the growing field documenting impaired cognition following mAMPH exposure, and constitute a rat model of the widely-reported decision-making deficits resulting from mAMPH abuse seen in humans.
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影响因子：
7.6
作者：
Belcher, AM;O'Dell, SJ;Marshall, JF
通讯作者：
Marshall, JF
影响因子：
7.6
作者：
Belcher, Annabelle M.;Feinstein, Erin M.;Marshall, John F.
通讯作者：
Marshall, John F.
DOI：
10.1017/sl461145706007395
发表时间：
2007-12-01
影响因子：
4.8
作者：
Chung, Ain;Lyoo, In Kyoon;Renshaw, Perry F.
通讯作者：
Renshaw, Perry F.
影响因子：
3.4
作者：
Fletcher, PJ;Tenn, CC;Kapur, S
通讯作者：
Kapur, S
影响因子：
2.5
作者：
GIBB, C;WILLOUGHBY, J;MARSDEN, CD
通讯作者：
MARSDEN, CD