Dorsal-striatal 5-HT2A and 5-HT2C receptors control impulsivity and perseverative responding in the 5-choice serial reaction Time Task
Dorsal-striatal 5-HT2A and 5-HT2C receptors control impulsivity and perseverative responding in the 5-choice serial reaction Time Task
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DOI：
10.1007/s00213-011-2581-0
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发表时间：
2012-01-01
影响因子：
3.4
通讯作者：
Carli, Mirjana
中科院分区：
文献类型：
--
作者：
Agnoli, Laura;Carli, Mirjana
理性前额叶皮质(PFC)和背侧纹状体是执行注意力的关键神经回路的一部分。5-羟色胺与注意和执行控制之间的关系是复杂的，这取决于实验条件和皮质纹状体核内不同5-羟色胺受体的激活水平。目的本研究探讨背内侧纹状体(dm-STR)中的哪两种5-HT2A和5-HT2C受体与阻断PFC内NMDA受体所致的执行注意缺陷有关。材料与结果采用五选一系列反应时任务(5-CSRTT)评估执行注意，该任务提供了注意力(准确性)以及执行控制表现的指标，如早熟(一个冲动的指标)和持续性反应。本实验观察了选择性5-羟色胺A拮抗剂M100907和L 1、3 mg/亩5-羟色胺2C激动剂Ro60-0175在dm-STR靶向注射100300 ng/亩L和1、3mU/亩L的作用。阻断NMDA受体会损害准确性和执行控制，表现为过早和持之以恒的反应增加。M100907和Ro60-0175均可剂量依赖性地预防CPP诱导的早熟和持续性过度反应。结论在背侧纹状体，5-羟色胺通过作用于5-HT2A和5-HT2C受体，可能整合了对5-CSRT任务执行的不同方面至关重要的谷氨酸皮质纹状体输入。
Rational Prefrontal cortex (PFC) and dorsal striatum are part of the neural circuit critical for executive attention. The relationship between 5-HT and aspects of attention and executive control is complex depending on experimental conditions and the level of activation of different 5-HT receptors within the nuclei of corticostriatal circuitry.Objective The present study investigated which 5-HT2A and 5-HT2C receptors in the dorsomedial-striatum (dm-STR) contribute to executive attention deficit induced by blockade of NMDA receptors in the PFC.Materials and results Executive attention was assessed by the five-choice serial reaction time task (5-CSRTT), which provides indices of attention (accuracy) and those of executive control over performance such as premature (an index of impulsivity) and perseverative responding. The effects of targeted infusion in dm-STR of 100 and 300 ng/mu l doses of the selective 5-HT2A antagonist M100907 and 1 and 3 mu g/mu l doses of 5-HT2C agonist Ro60-0175 was examined in animals injected with 50 ng/mu l dose of a competitive NMDA receptor antagonist 3-(R)-2-carboxypiperazin-4-phosphonic acid (CPP) in the mPFC. Blockade of NMDA receptors impaired accuracy as well as executive control as shown by increased premature and perseverative responding. The CPP-induced premature and perseverative over-responding were dose-dependently prevented by both M100907 and Ro60-0175. Both drugs partially removed the CPP-induced accuracy deficit but only at the highest dose tested.Conclusions It is suggested that in the dorsal striatum, 5-HT by an action on 5-HT2A and 5-HT2C receptors may integrate the glutamate corticostriatal inputs critical for different aspects of the 5-CSRT task performance.