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St-587和哌唑嗪对东莨菪碱处理大鼠水迷宫及被动回避行为的影响。

Effects of St-587 and prazosin on water maze and passive avoidance performance of scopolamine-treated rats.

作者信息

Puumala T, Sirviö J, Ruotsalainen S, Riekkinen P

机构信息

A.I. Virtanen Institute, University of Kuopio, Finland.

出版信息

Pharmacol Biochem Behav. 1996 Sep;55(1):107-15. doi: 10.1016/0091-3057(95)02231-7.

Abstract

The present experiments were designed to investigate whether the alpha-1 adrenergic and muscarinic cholinergic systems interact in the regulation of spatial navigation behavior in the Morris water maze test and passive avoidance performance. Pretraining administration of scopolamine, a muscarinic antagonist, markedly impaired the acquisition of water maze task (a hidden platform version) as well as retention of this task. The drug also impaired slightly navigation to a visible platform. Pretraining subcutaneous administration of St-587 (alpha-1 agonist) at 2000 micrograms/kg slightly improved the water maze navigation to a hidden platform in control rats, but its effect was not augmented in scopolamine-treated rats. Pretraining administration of prazosin (alpha-1 antagonist) 1000 micrograms/kg or 2000 micrograms/kg did not significantly potentiate the scopolamine (muscarinic cholinergic antagonist)-induced (doses 200 micrograms/kg and 100 micrograms/kg, pretraining intraperitoneal injection) deficit in water maze navigation. Pretraining administration of prazosin at doses 1000 micrograms/kg and 2000 micrograms/kg or St-587 at doses 1000 micrograms/kg and 2000 micrograms/kg did not have any significant influence on scopolamine-induced (200 micrograms/kg or 400 micrograms/kg) disruption in passive avoidance performance. These findings suggest that alpha-1 adrenergic mechanisms do not participate or are not the most important component of the noradrenergic system in the interaction between noradrenaline and muscarinic receptors in the modulation of learning and memory. The analysis of results indicates that activation of alpha-1 adrenoceptors might facilitate the acquisition of water maze task in its initial phase, for instance, switching from wall hugging strategy to an active exploration strategy. Furthermore, the present data suggest that muscarinic cholinergic blockade may affect both mnemonic and nonmnemonic processes in rats.

摘要

本实验旨在研究α-1肾上腺素能系统和毒蕈碱胆碱能系统在Morris水迷宫试验中空间导航行为调节及被动回避表现方面是否相互作用。毒蕈碱拮抗剂东莨菪碱的预训练给药显著损害了水迷宫任务(隐藏平台版本)的习得以及该任务的保持。该药物对可见平台的导航也有轻微损害。在对照大鼠中,预训练皮下注射2000微克/千克的St-587(α-1激动剂)可略微改善水迷宫中向隐藏平台的导航,但在东莨菪碱处理的大鼠中其效果并未增强。预训练腹腔注射1000微克/千克或2000微克/千克的哌唑嗪(α-1拮抗剂)并未显著增强东莨菪碱(毒蕈碱胆碱能拮抗剂,剂量为200微克/千克和100微克/千克,预训练腹腔注射)诱导的水迷宫导航缺陷。预训练给予1000微克/千克和2000微克/千克的哌唑嗪或1000微克/千克和2000微克/千克的St-587对东莨菪碱(200微克/千克或400微克/千克)诱导的被动回避表现破坏没有任何显著影响。这些发现表明,α-1肾上腺素能机制在去甲肾上腺素与毒蕈碱受体相互作用调节学习和记忆过程中不参与或不是去甲肾上腺素能系统的最重要组成部分。结果分析表明,α-1肾上腺素能受体的激活可能在水迷宫任务的初始阶段促进其习得,例如,从贴壁策略转变为主动探索策略。此外,目前的数据表明毒蕈碱胆碱能阻断可能会影响大鼠的记忆和非记忆过程。

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