Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific
Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific
复制标题
DOI：
10.1093/cercor/bhj120
复制
发表时间：
2007-01-01
期刊：
影响因子：
3.7
通讯作者：
Roberts, A. C.
中科院分区：
文献类型：
--
作者：
Clarke, H. F.;Walker, S. C.;Roberts, A. C.
我们先前已经证明，前额叶血清素的耗竭会损害眶额叶皮质（OFC）介导的系列辨别反转（SDR）学习，但不会损害外侧前额叶皮质（PFC）介导的注意定势转移。为了探究这种反转缺陷的神经化学特异性，实验1比较了OFC的选择性血清素耗竭和选择性多巴胺耗竭对SDR任务表现的影响。血清素耗竭显著损害了任务表现，而OFC多巴胺耗竭则没有影响。实验2通过研究OFC血清素耗竭对一种改良的SDR任务表现的影响来探究这种反转损伤的行为特异性，该改良任务旨在区分损伤的3种可能原因。结果表明，前额叶血清素耗竭导致的反转缺陷并非由于未能接近先前未受奖励的刺激（增强的习得性回避）或主动干扰减少。相反，它是由于未能抑制对先前受奖励刺激的反应。这种特定形式的认知不灵活性的神经化学和行为特异性与我们对许多涉及PFC的神经精神和神经退行性疾病中明显的不灵活行为的病因学和治疗的理解特别相关。
We have previously demonstrated that prefrontal serotonin depletion impairs orbitofrontal cortex (OFC)-mediated serial discrimination reversal (SDR) learning but not lateral prefrontal cortex (PFC)-mediated attentional set shifting. To address the neurochemical specificity of this reversal deficit, Experiment 1 compared the effects of selective serotonin and selective dopamine depletions of the OFC on performance of the SDR task. Whereas serotonin depletions markedly impaired performance, OFC dopamine depletions were without effect. The behavioral specificity of this reversal impairment was investigated in Experiment 2 by examining the effect of OFC serotonin depletion on performance of a modified SDR task designed to distinguish between 3 possible causes of the impairment. The results showed that the reversal deficit induced by prefrontal serotonin depletion was not due to a failure to approach a previously unrewarded stimulus (enhanced learned avoidance) or reduced proactive interference. Instead, it was due specifically to a failure to inhibit responding to the previously rewarded stimulus. The neurochemical and behavioral specificity of this particular form of cognitive inflexibility is of particular relevance to our understanding of the aetiology and treatment of inflexible behavior apparent in many neuropsychiatric and neurodegenerative disorders involving the PFC.