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六种假定的多巴胺受体激动剂对大鼠探究行为抑制作用的作用方式

On the mode of action of six putative dopamine receptor agonists on suppression of exploratory behaviour in rats.

作者信息

Ståhle L, Ungerstedt U

出版信息

Psychopharmacology (Berl). 1987;91(2):139-46. doi: 10.1007/BF00217053.

DOI:10.1007/BF00217053
PMID:3675730
Abstract

The effects of six putative dopamine receptor agonists on exploratory behaviour in rats were assessed: pergolide, (+)- and (-)-3-PPP, bromocriptine, mesulergine and CQ 32-084. Behaviour was automatically recorded in a holeboard apparatus and the data were analysed by the novel multivariate statistical method of partial least squares. All six substances suppressed exploratory behaviour at low doses. Pergolide and (+)-3-PPP-induced stereo-typed behaviour at higher doses. The suppression of exploration induced by pergolide was completely antagonised by sulpiride, partly antagonised by metoclopramide and weakly affected by haloperidol pretreatment. The effects of a low dose of (+)-3-PPP, bromocriptine or CQ 32-084, but not (-)-3-PPP or mesulergine, were antagonised by sulpiride. These findings support the hypotheses that pergolide, (+)-3-PPP, bromocriptine and CQ 32-084 inhibit exploration via stimulation of dopamine receptors. The present data do not substantiate the hypothesis that the suppression of exploration induced by (-)-3-PPP is mediated by stimulation of dopamine autoreceptors. A detailed analysis of the dose curves for pergolide and (+)-3-PPP indicates that the latter compound may have effects in addition to those of a dopamine receptor agonist.

摘要

评估了六种假定的多巴胺受体激动剂对大鼠探究行为的影响

培高利特、(+)-和(-)-3-PPP、溴隐亭、美舒麦角和CQ 32-084。行为在洞板装置中自动记录,数据采用偏最小二乘这种新的多元统计方法进行分析。所有六种物质在低剂量时均抑制探究行为。培高利特和(+)-3-PPP在较高剂量时诱导刻板行为。培高利特诱导的探究行为抑制被舒必利完全拮抗,被甲氧氯普胺部分拮抗,且受氟哌啶醇预处理的影响较弱。舒必利可拮抗低剂量(+)-3-PPP、溴隐亭或CQ 32-084的作用,但对(-)-3-PPP或美舒麦角无效。这些发现支持以下假设:培高利特、(+)-3-PPP、溴隐亭和CQ 32-084通过刺激多巴胺受体抑制探究行为。目前的数据并未证实(-)-3-PPP诱导的探究行为抑制是由多巴胺自身受体刺激介导的这一假设。对培高利特和(+)-3-PPP剂量曲线的详细分析表明,后一种化合物可能除了具有多巴胺受体激动剂的作用外还有其他作用。

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本文引用的文献

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Characterization of normal and supersensitive dopamine receptors: effects of ergot drugs and neuropeptides.正常和超敏多巴胺受体的特性:麦角药物和神经肽的作用
J Neural Transm. 1981;51(1-2):3-37. doi: 10.1007/BF01664003.
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The 'presynaptic' blocking potency of sulpiride and haloperidol in the rat is age-dependent.舒必利和氟哌啶醇在大鼠体内的“突触前”阻断效力具有年龄依赖性。
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阿扑吗啡诱导的大鼠打哈欠行为可被黑质的双侧6-羟基多巴胺损伤消除。
Psychopharmacology (Berl). 1987;93(3):336-42. doi: 10.1007/BF00187253.
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On the selectivity and specificity of the antagonism of apomorphine-induced suppression of exploration by sulpiride.关于舒必利对阿扑吗啡诱导的探索抑制作用拮抗的选择性和特异性
Psychopharmacology (Berl). 1989;99(1):75-9. doi: 10.1007/BF00634456.
5
Effects of low, autoreceptor selective doses of dopamine agonists on the discriminative cue and locomotor hyperactivity produced by d-amphetamine.低剂量、对自身受体有选择性的多巴胺激动剂对右旋苯丙胺产生的辨别性线索和运动性多动的影响。
J Neural Transm Gen Sect. 1991;86(1):61-70. doi: 10.1007/BF01250376.
通过记录大鼠的打哈欠行为评估阿扑吗啡、(+)-3-PPP和(-)-3-PPP的多巴胺自身受体激动剂特性。
Eur J Pharmacol. 1984 Feb 17;98(2):307-10. doi: 10.1016/0014-2999(84)90608-3.
4
Central dopamine receptor agonist and antagonist actions of the enantiomers of 3-PPP.3-PPP对映体的中枢多巴胺受体激动剂和拮抗剂作用。
Psychopharmacology (Berl). 1983;81(2):89-99. doi: 10.1007/BF00428999.
5
Effect of low-dose bromocriptine in treatment of psychosis: the dopamine autoreceptor-stimulation strategy.小剂量溴隐亭治疗精神病的效果:多巴胺自身受体刺激策略
Psychopharmacology (Berl). 1983;81(1):37-41. doi: 10.1007/BF00439271.
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Neurochemical effects of some ergot derivatives: a basis for their antiparkinson actions.某些麦角衍生物的神经化学效应:其抗帕金森作用的基础。
J Neural Transm. 1981;51(1-2):39-59. doi: 10.1007/BF01664004.
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Mesulergine and its 1,20-N,N-bidemethylated metabolite interact directly with D1- and D2-receptors.美舒麦角及其1,20-N,N-双去甲基代谢物直接与D1和D2受体相互作用。
Eur J Pharmacol. 1983 Nov 11;95(1-2):101-7. doi: 10.1016/0014-2999(83)90272-8.
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Interactions of ergot alkaloids with anterior pituitary D-2 dopamine receptors.麦角生物碱与垂体前叶D-2多巴胺受体的相互作用。
Mol Pharmacol. 1983 May;23(3):585-93.
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Low dose bromocriptine: a study of acute effects in chronic mediated schizophrenics.低剂量溴隐亭:对慢性介导型精神分裂症患者的急性效应研究
Prog Neuropsychopharmacol Biol Psychiatry. 1984;8(2):277-83. doi: 10.1016/0278-5846(84)90165-9.
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Evidence that apomorphine and pergolide induce rotation in rats by different actions on D1 and D2 receptor sites.阿扑吗啡和培高利特通过对D1和D2受体位点的不同作用诱导大鼠旋转的证据。
Eur J Pharmacol. 1984 Feb 17;98(2):165-76. doi: 10.1016/0014-2999(84)90587-9.