Sensitization to amphetamine, but not PCP, impairs attentional set shifting:: reversal by a D1 receptor agonist injected into the medial prefrontal cortex
Sensitization to amphetamine, but not PCP, impairs attentional set shifting:: reversal by a D1 receptor agonist injected into the medial prefrontal cortex
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DOI：
10.1007/s00213-005-0157-6
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发表时间：
2005-12-01
影响因子：
3.4
通讯作者：
Kapur, S
中科院分区：
文献类型：
--
作者：
Fletcher, PJ;Tenn, CC;Kapur, S
基本原理：反复接触精神兴奋剂可导致对其作用的敏感化，而敏感化与精神分裂症和药物滥用的病理生理学有关。这些疾病的特征在于认知缺陷，特别是在前额介导的执行功能。目的：本实验研究了苯丙胺和苯环己哌啶（PCP）的敏化方案对注意定势转移的影响。方法：大鼠分别注射苯丙胺、PCP或生理盐水，每周3次，共5周。四周后，老鼠被训练在两个碗中的一个碗中挖掘食物，每个碗都有一种气味和质地。只有一个维度（气味或质地）能正确预测哪个碗被放了饵。然后对大鼠进行一系列的辨别测试，包括那些需要维内移位（IDS）、维外移位（EDS）或先前相关和不相关刺激的逆转的辨别测试。结果：苯丙胺致敏大鼠在IDS上表现正常，但在EDS和反转辨别上受损。PCP致敏大鼠的任何歧视不受影响。在安非他明致敏大鼠的EDS阶段的赤字被逆转的D-1受体激动剂SKF 38393注入内侧前额叶皮层（mPFC）。结论：结果表明，安非他明敏化状态损害前额叶介导的注意定势转移。这与精神分裂症和成瘾中的认知缺陷一致，并且与安非他明致敏伴随mPFC功能变化的证据一致。这些结果进一步增加了越来越多的文献，表明激活mPFC中的D1受体可以改善认知方面。
Rationale: Repeated exposure to psychomotor stimulants can lead to sensitization to their effects, and sensitization has been implicated in the pathophysiology of schizophrenia and drug abuse. These disorders are characterized by cognitive deficits, particularly in prefrontally mediated executive function. Objective: The present experiments were conducted to investigate the effects of sensitizing regimens of amphetamine and phencyclidine (PCP) on attentional set shifting. Methods: Rats received injections of amphetamine, PCP or saline three times per week for 5 weeks. Four weeks later, rats were trained to dig for food in one of two bowls, each bowl having an odour and a texture. Only one dimension (odour or texture) correctly predicted which bowl was baited. Rats were then tested on a series of discriminations including those requiring an intra-dimensional shift (IDS), an extra-dimensional shift (EDS) or a reversal of previously relevant and irrelevant stimuli. Results: Rats sensitized to amphetamine performed normally on the IDS, but were impaired on the EDS, as well as on reversal discriminations. PCP-sensitized rats were unaffected on any of the discriminations. In amphetamine-sensitized rats the deficit at the EDS stage was reversed by infusion of the D-1 receptor agonist SKF38393 into the medial prefrontal cortex (mPFC). Conclusions: Results show that the amphetamine-sensitized state impairs prefrontally mediated attentional set shifting. This is consistent with cognitive deficits in schizophrenia and addiction, and with the evidence that amphetamine sensitization is accompanied by functional changes in the mPFC. These results further add to a growing literature showing that activating D, receptors in the mPFC improves aspects of cognition.