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选择性和非选择性多巴胺激动剂诱导大鼠攀爬的能力差异表明,D-1和D-2受体均参与了这一行为。

Differential ability of selective and non-selective dopamine agonists to induce climbing in the rat indicates the involvement of both D-1 and D-2 receptors in this behaviour.

作者信息

Davis A, Jenner P, Marsden C D

机构信息

MRC Movement Disorders Research Group, University Department of Neurology, London, UK.

出版信息

Psychopharmacology (Berl). 1990;100(1):19-26. doi: 10.1007/BF02245783.

Abstract

Approximately 50% of female Wistar rats examined exhibited a continuous climbing response to a screening dose of apomorphine. In animals identified as climbing, the mixed D-1/D-2 agonists apomorphine, pergolide and L-dopa, and the indirectly acting agonists nomifensine and (+)-amphetamine, induced a dose-related climbing response. The selective D-1 agonist SKF 38393 caused only minimal climbing, and the selective D-2 agonists bromocriptine, lisuride and LY 141865 induced a weak climbing response. All agonists examined, except SKF 38393, caused a dose-related stereotypy response. The selective D-1 antagonist SCH 23390, and the selective D-2 antagonist sulpiride, both produced maximum inhibition of apomorphine-induced climbing. SCH 23390 also inhibited stereotyped behaviour, but sulpiride was less effective. In animals identified as "non-climbers" using the screening dose of apomorphine, only L-dopa induced a marked climbing response. Nomifensine and bromocriptine produced weak or discontinuous climbing in this group, while the other agonists examined had little or no effect. In contrast all drugs examined, except SKF 38393, induced stereotyped behaviour of the same intensity observed in the "climbers". It is concluded that stimulation of both D-1 and D-2 receptors is necessary to induce a continuous climbing behaviour in rats. D-2, but not D-1 stimulation, alone can induce a weak or discontinuous climbing response, but concomitant stimulation of D-1 receptors potentiates this effect. Failure of some rats to climb does not appear to be related to relative degrees of D-1 and D-2 stimulation.

摘要

在接受阿扑吗啡筛选剂量检测的雌性Wistar大鼠中,约50%表现出对该剂量阿扑吗啡的持续攀爬反应。在被鉴定为有攀爬反应的动物中,D-1/D-2混合型激动剂阿扑吗啡、培高利特和左旋多巴,以及间接作用激动剂诺米芬辛和(+)-苯丙胺,均能诱导出剂量相关的攀爬反应。选择性D-1激动剂SKF 38393仅引起极轻微的攀爬反应,而选择性D-2激动剂溴隐亭、利舒脲和LY 141865则诱导出较弱的攀爬反应。除SKF 38393外,所有检测的激动剂均能引起剂量相关的刻板反应。选择性D-1拮抗剂SCH 23390和选择性D-2拮抗剂舒必利,均能最大程度抑制阿扑吗啡诱导的攀爬反应。SCH 23390也能抑制刻板行为,但舒必利的效果较差。在使用阿扑吗啡筛选剂量鉴定为“无攀爬反应”的动物中,只有左旋多巴能诱导出明显的攀爬反应。诺米芬辛和溴隐亭在该组中引起较弱或不连续的攀爬反应,而其他检测的激动剂几乎没有或没有效果。相比之下,除SKF 38393外,所有检测的药物均能诱导出与“有攀爬反应”组中观察到的强度相同的刻板行为。得出的结论是,刺激D-1和D-2受体对于诱导大鼠持续攀爬行为是必要的。单独刺激D-2受体而非D-1受体,可诱导出较弱或不连续的攀爬反应,但同时刺激D-1受体可增强这种效果。一些大鼠不出现攀爬反应似乎与D-1和D-2受体的相对刺激程度无关。

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