Opposing effects of 5-HT2A and 5-HT2C receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time test
Opposing effects of 5-HT2A and 5-HT2C receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time test
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DOI：
10.1007/s00213-007-0891-z
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发表时间：
2007-12-01
影响因子：
3.4
通讯作者：
Higgins, Guy A.
中科院分区：
文献类型：
--
作者：
Fletcher, Paul J.;Tampakeras, Maria;Higgins, Guy A.
理论基础5-羟色胺(5-HT)与冲动有关，最近的数据表明，不同的受体亚型对这种行为产生相反的影响。目的本工作表征了5-羟色胺(5-羟色胺，(+/-)2，3-dimethoxyphenyl-1-[2-4-(piperidine)methanol][M100907])的作用，5-HT2B(6-氯-5-甲基-1(5-喹啉氨甲酰基)吲哚[SB215505]和5-HT2C(6-chloro-5-methyl-1-[2-(2-methylpyridyl-3-oxy)-pyrid-5-yl氨甲酰基]吲哚[SB242084])受体拮抗剂对大鼠和小鼠冲动行为的影响。实验还检测了被广泛用作5-羟色胺和5-羟色胺2C受体激动剂的(+/-)-2，5-二甲氧基-4-碘苯丙胺和(S)-2(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1：1 C4H4O4(Ro60-0175)的作用。材料与方法对大鼠和小鼠进行5CSRTT训练，在5CSRTT中获得增强以检测并正确地对短暂的刺激光做出反应。在这项任务中，冲动是指在刺激呈现之前过早做出反应。这项任务的几个变种被使用，其中操纵试验间间隔(ITI)长度来改变早熟反应的基础水平。结果在大鼠中，酮丝林和M100907减少，SB242084增强早熟反应。SB215505不起作用。DOI通常会扰乱反应，而Ro600175在使用较长ITI时减少了过早反应。在小鼠中，当ITI延长时，M100907减少，SB242084增加过早反应。这些药物对其他方面表现的影响就不那么明显了。M100907和Ketanserin对反应的准确性没有影响，但有减慢反应速度的趋势；SB242084有时加快反应的速度，略有降低的准确性。结论5-羟色胺通过5-HT2A和5-HT2C受体对大鼠和小鼠的运动冲动产生兴奋和抑制作用。
Rationale Serotonin (5-HT) has been linked to impulsivity with recent data suggesting that different receptor sub-types exert opposing influences on this behaviour.Objectives This work characterised the effects of 5-HT2A (ketanserin, (+/-)2,3-dimethoxyphenyl-1-[2-4-(piperidine)methanol] [M100907]), 5-HT2B (6-chloro-5-methyl-1(5-quinolylcarbamoyl) indoline [SB215505]) and 5-HT2C (6-chloro-5-methyl-1-[2-(2-methylpyridyl-3-oxy)-pyrid-5-yl carbomyl] indoline [SB242084]) receptor antagonists on impulsive behaviour, measured in the five-choice serial reaction time test (5CSRTT), in rats and mice. The effects of (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI)and (S)-2(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1: 1 C4H4O4 (Ro60-0175), two compounds that have been used extensively as agonists for the 5-HT2A and 5-HT2C receptor, were also measured.Materials and methods Rats and mice were trained on the 5CSRTT in which reinforcement is earned for detecting and correctly responding to brief presentations of a stimulus light. Impulsivity in this task is measured as premature responding, before stimulus presentation. Several variants of the task were used in which the inter-trial interval (ITI) length was manipulated to alter basal levels of premature responding.Results In the rat, ketanserin and M100907 reduced and SB242084 enhanced premature responding. SB215505 had no effect. DOI generally disrupted responding, while Ro600175 reduced premature responding when a long ITI was used. In mice, M100907 reduced and SB242084 increased premature responding when the ITI was lengthened. The effects of these drugs on other aspects of performance were less robust. M100907 and ketanserin did not affect response accuracy but tended to slow speed of responding; SB242084 occasionally increased speed of responding and slightly reduced accuracy.Conclusions Serotonin exerts both excitatory and inhibitory influences on motor impulsivity via 5-HT2A and 5-HT2C receptors in both rats and mice.