• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

中枢5-羟色胺耗竭对d-苯丙胺间隔计时行为效应的减弱作用。

Attenuation of the effects of d-amphetamine on interval timing behavior by central 5-hydroxytryptamine depletion.

作者信息

Body S, Cheung T H C, Hampson C L, den Boon F S, Bezzina G, Fone K C F, Bradshaw C M, Szabadi E

机构信息

Psychopharmacology Section, Division of Psychiatry, Medical School, Queen's Medical Centre, University of Nottingham, Room B109, Nottingham NG7 2UH, UK.

出版信息

Psychopharmacology (Berl). 2009 Apr;203(3):547-59. doi: 10.1007/s00213-008-1400-8. Epub 2008 Nov 19.

DOI:10.1007/s00213-008-1400-8
PMID:19018519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2761547/
Abstract

RATIONALE

Interval timing in the free-operant psychophysical procedure is sensitive to the monoamine-releasing agent d-amphetamine, the D(2)-like dopamine receptor agonist quinpirole, and the D(1)-like agonist 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzepine (SKF-81297). The effect of d-amphetamine can be antagonized by selective D(1)-like and 5-HT(2A) receptor antagonists. It is not known whether d-amphetamine's effect requires an intact 5-hydroxytryptamine (5-HT) pathway.

OBJECTIVE

The objective of this study was to examine the effects of d-amphetamine, quinpirole, and SKF-81297 on timing in intact rats and rats whose 5-hydroxytryptaminergic (5-HTergic) pathways had been ablated.

MATERIALS AND METHODS

Rats were trained under the free-operant psychophysical procedure to press levers A and B in 50-s trials in which reinforcement was provided intermittently for responding on A in the first half, and B in the second half of the trial. Percent responding on B (%B) was recorded in successive 5-s epochs of the trials; logistic functions were fitted to the data for derivation of timing indices (T(50), time corresponding to %B = 50%; Weber fraction). The effects of d-amphetamine (0.4 mg kg(-1) i.p.), quinpirole (0.08 mg kg(-1) i.p.), and SKF-81297 (0.4 mg kg(-1) s.c.) were compared between intact rats and rats whose 5-HTergic pathways had been destroyed by intra-raphe injection of 5,7-dihydroxytryptamine.

RESULTS

Quinpirole and SKF-81297 reduced T(50) in both groups; d-amphetamine reduced T(50) only in the sham-lesioned group. The lesion reduced 5-HT levels by 80%; catecholamine levels were not affected.

CONCLUSIONS

d-Amphetamine's effect on performance in the free-operant psychophysical procedure requires an intact 5-HTergic system. 5-HT, possibly acting at 5-HT(2A) receptors, may play a 'permissive' role in dopamine release.

摘要

原理

在自由操作心理物理学程序中的间隔计时对单胺释放剂d-苯丙胺、D(2)样多巴胺受体激动剂喹吡罗以及D(1)样激动剂6-氯-2,3,4,5-四氢-1-苯基-1H-3-苯并氮杂卓（SKF-81297）敏感。d-苯丙胺的作用可被选择性D(1)样和5-HT(2A)受体拮抗剂拮抗。尚不清楚d-苯丙胺的作用是否需要完整的5-羟色胺（5-HT）通路。

目的

本研究的目的是研究d-苯丙胺、喹吡罗和SKF-81297对完整大鼠以及5-羟色胺能（5-HT能）通路已被损毁的大鼠计时的影响。

材料与方法

在自由操作心理物理学程序下训练大鼠，在50秒的试验中按压杠杆A和B，其中在前半段试验中对按压A给予间歇性强化，后半段试验中对按压B给予强化。在试验连续的5秒时间段内记录对B的反应百分比（%B）；将逻辑函数拟合到数据中以推导计时指标（T(50)，对应%B = 50%的时间；韦伯分数）。比较d-苯丙胺（0.4 mg kg(-1)腹腔注射）、喹吡罗（0.08 mg kg(-1)腹腔注射）和SKF-81297（0.4 mg kg(-1)皮下注射）对完整大鼠和中缝内注射5,7-二羟基色胺损毁了5-HT能通路的大鼠的影响。

结果

喹吡罗和SKF-81297在两组中均降低了T(50)；d-苯丙胺仅在假损毁组中降低了T(50)。损毁使5-HT水平降低了80%；儿茶酚胺水平未受影响。

结论

d-苯丙胺对自由操作心理物理学程序中行为表现的影响需要完整的5-HT能系统。5-HT可能通过作用于5-HT(2A)受体，在多巴胺释放中发挥“允许”作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/71b2d97734fe/213_2008_1400_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/6afb4e416977/213_2008_1400_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/667743c0585a/213_2008_1400_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/35e51e1ef5a5/213_2008_1400_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/f0752f09ee47/213_2008_1400_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/e7b4f38d29b5/213_2008_1400_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/71b2d97734fe/213_2008_1400_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/6afb4e416977/213_2008_1400_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/667743c0585a/213_2008_1400_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/35e51e1ef5a5/213_2008_1400_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/f0752f09ee47/213_2008_1400_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/e7b4f38d29b5/213_2008_1400_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2761547/71b2d97734fe/213_2008_1400_Fig6_HTML.jpg

相似文献

1
Attenuation of the effects of d-amphetamine on interval timing behavior by central 5-hydroxytryptamine depletion.中枢5-羟色胺耗竭对d-苯丙胺间隔计时行为效应的减弱作用。
Psychopharmacology (Berl). 2009 Apr;203(3):547-59. doi: 10.1007/s00213-008-1400-8. Epub 2008 Nov 19.
2
Effects of d-amphetamine and DOI (2,5-dimethoxy-4-iodoamphetamine) on timing behavior: interaction between D1 and 5-HT2A receptors.右旋苯丙胺和DOI（2,5-二甲氧基-4-碘苯丙胺）对定时行为的影响：D1与5-HT2A受体之间的相互作用
Psychopharmacology (Berl). 2006 Dec;189(3):331-43. doi: 10.1007/s00213-006-0575-0. Epub 2006 Oct 19.
3
Failure of central 5-hydroxytryptamine depletion to alter the effect of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on timing performance on the free-operant psychophysical procedure.中枢5-羟色胺耗竭未能改变8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）对自由操作心理物理学程序中定时表现的影响。
Psychopharmacology (Berl). 2001 Nov;158(3):305-13. doi: 10.1007/s002130100886.
4
Evidence for the sensitivity of operant timing behaviour to stimulation of D1 dopamine receptors.操作性定时行为对D1多巴胺受体刺激敏感性的证据。
Psychopharmacology (Berl). 2007 Dec;195(2):213-22. doi: 10.1007/s00213-007-0892-y. Epub 2007 Aug 1.
5
Effects of fenfluramine on free-operant timing behaviour: evidence for involvement of 5-HT2A receptors.芬氟拉明对自由操作定时行为的影响：5-HT2A 受体参与的证据。
Psychopharmacology (Berl). 2004 Nov;176(2):154-65. doi: 10.1007/s00213-004-1871-1. Epub 2004 Apr 22.
6
Evidence for a role of D1 dopamine receptors in d-amphetamine's effect on timing behaviour in the free-operant psychophysical procedure.D1多巴胺受体在右旋苯丙胺对自由操作心理物理学程序中时间行为影响方面作用的证据。
Psychopharmacology (Berl). 2006 Apr;185(3):378-88. doi: 10.1007/s00213-006-0339-x. Epub 2006 Mar 15.
7
Tolerance to the effect of 2,5-dimethoxy-4-iodoamphetamine (DOI) on free-operant timing behaviour: interaction between behavioural and pharmacological mechanisms.对2,5-二甲氧基-4-碘苯丙胺（DOI）对自由操作定时行为影响的耐受性：行为和药理机制之间的相互作用。
Psychopharmacology (Berl). 2007 Jul;192(4):521-35. doi: 10.1007/s00213-007-0743-x. Epub 2007 Mar 2.
8
Effect of quinpirole on timing behaviour in the free-operant psychophysical procedure: evidence for the involvement of D2 dopamine receptors.喹吡罗对自由操作心理物理学程序中定时行为的影响：D2多巴胺受体参与的证据
Psychopharmacology (Berl). 2007 Aug;193(3):423-36. doi: 10.1007/s00213-007-0798-8. Epub 2007 May 6.
9
The effect of d-amphetamine on performance on two operant timing schedules.右旋苯丙胺对两种操作性定时程序表现的影响。
Psychopharmacology (Berl). 2000 Jun;150(2):170-84. doi: 10.1007/s002130000422.
10
Antagonism by WAY-100635 of the effects of 8-OH-DPAT on performance on a free-operant timing schedule in intact and 5-HT-depleted rats.WAY-100635对8-OH-DPAT在完整和5-羟色胺缺乏大鼠自由操作定时程序中行为表现影响的拮抗作用。
Behav Pharmacol. 2002 Dec;13(8):603-14. doi: 10.1097/00008877-200212000-00001.

引用本文的文献

1
Amphetamine increases timing variability by degrading prefrontal temporal encoding.苯丙胺通过破坏前额叶时间编码来增加时间变异性。
Neuropharmacology. 2025 Sep 1;275:110486. doi: 10.1016/j.neuropharm.2025.110486. Epub 2025 May 3.
2
The Role of the Serotonergic System in Time Perception: A Systematic Review.血清素能系统在时间感知中的作用：一项系统综述。
Int J Mol Sci. 2024 Dec 11;25(24):13305. doi: 10.3390/ijms252413305.
3
Reward-enhancing effects of d-amphetamine and its interactions with nicotine were greater in female rats and persisted across schedules of reinforcement.

本文引用的文献

1
The influence of `switching' on the psychometric function in the free-operant psychophysical procedure.
Behav Processes. 1998 Dec;44(2):197-209. doi: 10.1016/s0376-6357(98)00049-7.
2
Guide to Receptors and Channels (GRAC), 3rd edition.《受体与通道指南》（GRAC），第三版。
Br J Pharmacol. 2008 Mar;153 Suppl 2(Suppl 2):S1-209. doi: 10.1038/sj.bjp.0707746.
3
Evidence for the sensitivity of operant timing behaviour to stimulation of D1 dopamine receptors.操作性定时行为对D1多巴胺受体刺激敏感性的证据。
安非他命和尼古丁的奖励增强效应在雌性大鼠中更为明显，并在强化计划中持续存在。
Behav Pharmacol. 2021 Aug 1;32(5):435-447. doi: 10.1097/FBP.0000000000000637.
4
Premature responses in the five-choice serial reaction time task reflect rodents' temporal strategies: evidence from no-light and pharmacological challenges.五选择连续反应时任务中的过早反应反映了啮齿动物的时间策略：来自无光和药理学挑战的证据。
Psychopharmacology (Berl). 2016 Oct;233(19-20):3513-25. doi: 10.1007/s00213-016-4389-4. Epub 2016 Aug 17.
5
Subjective and Real Time: Coding Under Different Drug States.主观与实时：不同药物状态下的编码
Int J Comp Psychol. 2015;28.
6
Effect of 5-HT2A and 5-HT2C receptors on temporal discrimination by mice.5-羟色胺2A和5-羟色胺2C受体对小鼠时间辨别能力的影响。
Neuropharmacology. 2016 Aug;107:364-375. doi: 10.1016/j.neuropharm.2016.03.038. Epub 2016 Mar 25.
7
Consideration of species differences in developing novel molecules as cognition enhancers.考虑物种差异在开发新型分子作为认知增强剂方面的作用。
Neurosci Biobehav Rev. 2013 Nov;37(9 Pt B):2181-93. doi: 10.1016/j.neubiorev.2012.10.002. Epub 2012 Oct 12.
8
Fos expression in the prefrontal cortex and ventral striatum after exposure to a free-operant timing schedule.暴露于自由操作定时程序后前额皮质和腹侧纹状体中的 Fos 表达。
Behav Brain Res. 2012 Dec 1;235(2):273-9. doi: 10.1016/j.bbr.2012.08.009. Epub 2012 Aug 16.
9
Performance deficits of NK1 receptor knockout mice in the 5-choice serial reaction-time task: effects of d-amphetamine, stress and time of day.NK1 受体敲除小鼠在 5 -choice 连续反应时任务中的表现缺陷：安非他命、应激和时间的影响。
PLoS One. 2011 Mar 7;6(3):e17586. doi: 10.1371/journal.pone.0017586.
10
Relative time sharing: new findings and an extension of the resource allocation model of temporal processing.相对时间分配：新发现及时间处理资源分配模型的扩展
Philos Trans R Soc Lond B Biol Sci. 2009 Jul 12;364(1525):1875-85. doi: 10.1098/rstb.2009.0022.
Psychopharmacology (Berl). 2007 Dec;195(2):213-22. doi: 10.1007/s00213-007-0892-y. Epub 2007 Aug 1.
4
Effect of quinpirole on timing behaviour in the free-operant psychophysical procedure: evidence for the involvement of D2 dopamine receptors.喹吡罗对自由操作心理物理学程序中定时行为的影响：D2多巴胺受体参与的证据
Psychopharmacology (Berl). 2007 Aug;193(3):423-36. doi: 10.1007/s00213-007-0798-8. Epub 2007 May 6.
5
Tolerance to the effect of 2,5-dimethoxy-4-iodoamphetamine (DOI) on free-operant timing behaviour: interaction between behavioural and pharmacological mechanisms.对2,5-二甲氧基-4-碘苯丙胺（DOI）对自由操作定时行为影响的耐受性：行为和药理机制之间的相互作用。
Psychopharmacology (Berl). 2007 Jul;192(4):521-35. doi: 10.1007/s00213-007-0743-x. Epub 2007 Mar 2.
6
Effects of d-amphetamine and DOI (2,5-dimethoxy-4-iodoamphetamine) on timing behavior: interaction between D1 and 5-HT2A receptors.右旋苯丙胺和DOI（2,5-二甲氧基-4-碘苯丙胺）对定时行为的影响：D1与5-HT2A受体之间的相互作用
Psychopharmacology (Berl). 2006 Dec;189(3):331-43. doi: 10.1007/s00213-006-0575-0. Epub 2006 Oct 19.
7
Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission.血清素对多巴胺神经传递调节的药理学机制。
Pharmacol Ther. 2007 Feb;113(2):296-320. doi: 10.1016/j.pharmthera.2006.08.004. Epub 2006 Oct 17.
8
Neuroanatomical localization of an internal clock: a functional link between mesolimbic, nigrostriatal, and mesocortical dopaminergic systems.内部时钟的神经解剖学定位：中脑边缘、黑质纹状体和中脑皮质多巴胺能系统之间的功能联系。
Brain Res. 2006 Sep 13;1109(1):93-107. doi: 10.1016/j.brainres.2006.06.031. Epub 2006 Aug 4.
9
The behavioral theory of timing: Reinforcer rate determines pacemaker rate.行为时间理论：强化物率决定着节拍器率。
J Exp Anal Behav. 1994 Jan;61(1):19-33. doi: 10.1901/jeab.1994.61-19.
10
Scaling of stimulus duration by pigeons.鸽子对刺激时长的缩放。
J Exp Anal Behav. 1976 Jul;26(1):15-25. doi: 10.1901/jeab.1976.26-15.