Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capability
Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capability
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DOI：
10.1016/j.neuroscience.2005.09.031
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Morilak, DA
中科院分区：
文献类型：
--
作者：
Lapiz, MDS;Morilak, DA
大脑去甲肾上腺素系统被认为促进神经过程，促进行为激活、警觉性和注意力。去甲肾上腺素可能发挥这种作用的一个区域是内侧前额叶皮质，它参与了许多认知功能，包括唤醒、注意力、动机、工作记忆、反应抑制和行为灵活性。本研究探讨了内侧前额叶皮质去甲肾上腺素能神经传递对大鼠认知功能的调制影响，通过注意定势转移任务中的表现来衡量。在实验1中，我们测试了全身应用α(2)-肾上腺素能自身受体拮抗剂和激动剂阿替帕唑和可乐定分别增加和减少去甲肾上腺素能神经递质的作用。在需要注意向外转移的注意任务和涉及刺激反转的注意任务阶段，阿替帕唑预处理显著改善了表现，而可乐定在任何阶段都没有影响。在实验2中，我们测试了内侧前额叶皮质微量注射α(1)或β-肾上腺素能受体拮抗剂对提高由阿替普奈唑产生的外显任务成绩的影响。内侧前额叶皮质的α(1)受体拮抗剂可阻断阿替帕唑诱导的外向定势转换作业成绩的增强，而β-肾上腺素能受体拮抗剂不能阻断这种增强作用。两种拮抗剂在没有阿替帕唑诱导增强的情况下，对外周SET漂移表现没有任何影响。这些结果表明，提高内侧前额叶皮质α(1)受体的去甲肾上腺素活性有助于大鼠在注意定势转移任务中的认知表现，这可能有助于去甲肾上腺素在行为状态变化(如唤醒)中的作用，或有助于以去甲肾上腺素能神经传递为靶点的心理治疗药物的有益认知效果。(C)2005年由爱思唯尔有限公司代表IBRO出版。
The brain noradrenergic system is thought to facilitate neuronal processes that promote behavioral activation, alertness, and attention. One region in which norepinephrine may exert such effects is the medial prefrontal cortex, which has been implicated in many cognitive functions including arousal, attention, motivation, working memory, response inhibition, and behavioral flexibility. The present study addressed the modulatory influence of noradrenergic neurotransmission in medial prefrontal cortex on cognitive function in rats, as measured by performance in an attentional set shifting task. In experiment 1, we tested effects of increasing and decreasing brain noradrenergic neurotransmission by systemic administration of the alpha(2)-adrenergic autoreceptor antagonist and agonist drugs, atipamezole and clonidine, respectively. Atipamezole pretreatment significantly improved performance on the stages of the attentional task requiring an extradimensional shift in attention, and those involving stimulus reversals, whereas clonidine had no effect at any stage. In experiment 2, we then tested effects of microinjecting alpha(1)- or beta-adrenergic receptor antagonists into medial prefrontal cortex on the enhancement of performance on the extradimensional task produced by atiparnezole. The atipamezole-induced enhancement of performance on the extradimensional set shifting task was blocked by alpha(1)-, but not beta-adrenergic receptor antagonists in medial prefrontal cortex. Neither antagonist alone had any effect on extradimensional set shift performance in the absence of atipamezole-induced enhancement. These results indicate that elevating noradrenergic activity at alpha(1)-receptors in medial prefrontal cortex facilitates cognitive performance of rats in an attentional set-shifting task, which may contribute to the role of norepinephrine in behavioral state changes such as arousal, or to the beneficial cognitive effects of psychotherapeutic drugs that target noradrenergic neurotransmission. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.