Amphetamine exposure selectively enhances hippocampus-dependent spatial learning and attenuates amygdala-dependent cue learning.
Amphetamine exposure selectively enhances hippocampus-dependent spatial learning and attenuates amygdala-dependent cue learning.
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DOI：
10.1038/npp.2010.14
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发表时间：
2010-06
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--
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安非他明暴露的行为敏化方案对学习、记忆和认知具有不同的影响，这可能是皮质-边缘-纹状体回路中发生的长期神经适应的结果。特别是，多巴胺信号在丘脑核和内侧前额叶皮层的改变与安非他明诱导的行为变化有关。本研究试图验证这一假设，即反复接触安非他明破坏了边缘系统信息处理的调节和竞争性边缘系统控制食欲行为的平衡。小鼠接受了7次d-苯丙胺的腹膜内注射（2.5mg/kg或5 mg/kg）或载体溶液（盐水），并在1）使用6臂径向迷宫的同时条件提示和位置偏好任务中训练，发现其分别依赖于海马（HPC）和基底外侧杏仁核（BLA）的完整性，和2）条件BLA-dependent提示-，和使用高架T-迷宫的HPC依赖性位置学习任务。在这两个任务中，车辆预处理组获得线索学习第一，其次是显着的地方/空间学习的出现。与此相反，预处理与重复安非他明造成显着偏离正常的收购模式的地方和线索条件，显着促进HPC依赖的地方条件在第一个任务，而衰减BLA依赖的线索条件在这两个任务。这些研究结果提供了第一个演示的异常调节HPC和BLA-dependent学习作为安非他明暴露的结果，突出了中coticolimbic多巴胺系统在维持边缘系统控制食欲行为的平衡的重要性。
Behaviorally sensitizing regimen of amphetamine exposure has diverse effects on learning, memory and cognition that is likely to be a consequence of long term neural adaptations occurring in the cortico-limbic-striatal circuitry. In particular, altered dopamine signaling in the nucleus accumbens and medial prefrontal cortex has been implicated to underlie amphetamine-induced changes in behavior. The present study sought to test the hypothesis that repeated amphetamine exposure disrupts the regulation of limbic information processing and the balance of competing limbic control over appetitive behavior. Mice received 7 intra-peritoneal injections of d-amphetamine (2.5mg/kg or 5mg/kg) or vehicle solution (saline) and were trained in a 1) simultaneous conditioned cue and place preference task using a 6 arm radial maze, found to depend upon the integrity of the hippocampus (HPC), and basolateral amygdala (BLA) respectively and a 2) conditional BLA-dependent cue-, and HPC-dependent place learning task using an elevated T-maze. In both tasks, the vehicle pre-treatment group acquired cue learning first, followed by the emergence of significant place/spatial learning. In contrast, pre-treatment with repeated amphetamine caused marked deviations from normal acquisition patterns of place and cue conditioning, significantly facilitating HPC-dependent place conditioning in the first task, while attenuating BLA-dependent cue conditioning in both tasks. These findings provide the first demonstration of aberrant regulation of HPC and BLA-dependent learning as a result of amphetamine exposure, highlighting the importance of the meso-coticolimbic dopamine system in maintaining the balance of limbic control over appetitive behavior.
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影响因子：
10.6
作者：
Castner, SA;Goldman-Rakic, PS
通讯作者：
Goldman-Rakic, PS
影响因子：
3.3
作者：
EVERITT, BJ;MORRIS, KA;ROBBINS, TW
通讯作者：
ROBBINS, TW
影响因子：
3.3
作者：
Bjijou, Y;De Deurwaerdere, P;Cador, M
通讯作者：
Cador, M
影响因子：
5.3
作者：
Floresco, SB;Blaha, CD;Phillips, AG
通讯作者：
Phillips, AG
影响因子：
16.2
作者：
Goto, Y;Grace, AA
通讯作者：
Grace, AA