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强迫游泳诱导的应激对5-羟色胺(1A)类药物抗焦虑样作用在小鼠中的影响。

Influence of forced swimming-induced stress on the anxiolytic-like effect of 5HT(1A) agents in mice.

作者信息

Briones-Aranda A, López-Rubalcava C, Picazo O

机构信息

Escuela Superior de Medicina, I.P.N., Plan de San Luis y Diaz Mirón, Col. Sto. Tomás, México D.F.11340, México.

出版信息

Psychopharmacology (Berl). 2002 Jul;162(2):147-55. doi: 10.1007/s00213-002-1046-x. Epub 2002 May 15.

DOI:10.1007/s00213-002-1046-x
PMID:12110992
Abstract

RATIONALE

Stress has been related to both anxiety and mood disorders. Forced swimming (FS) is a type of stress that is able to modify the activity of serotonin (5-HT) and GABA in the central nervous system. 5-HT(1A) compounds have been shown to be anxiolytic in a variety of behavioral models and in clinical studies.

OBJECTIVE

The main purpose of the present study was to analyze the effect of FS on the anxiolytic-like actions of three 5-HT(1A) compounds.

METHODS

Stressed (ST) and unstressed (UST) mice were evaluated in the exploratory behavior test (EBT) or burying behavior test (BBT). In addition, the action of increasing doses of the 5-HT(1A) compounds buspirone, 8-OH-DPAT and indorenate in ST and UST mice was analyzed using the EBT. A spontaneous ambulatory behavior test was carried out immediately after the anxiety tests.

RESULTS

One session of FS induced anxiolytic-like behavior in mice tested in both the EBT and the BBT. This effect of FS was blocked by a previous administration of either picrotoxin or WAY 100635. The 5-HT(1A) compounds produced a clear anxiolytic-like effect in UST animals. By contrast, with low doses of either 8-OH-DPAT (0.01 mg/kg), buspirone (0.03 mg/kg) or indorenate (0.3, 0.6 mg/kg) ST mice showed a decrease in the anti-anxiety-like effect observed after FS. No change in ambulation that could mask the results of the anxiety test was registered.

CONCLUSIONS

The present data provide evidence that FS induces changes in the effect of 5-HT(1A) agents. The participation of the 5-HT and/or GABA systems in these stress-induced effects is discussed.

摘要

原理

应激与焦虑症和情绪障碍均相关。强迫游泳(FS)是一种能够改变中枢神经系统中血清素(5-HT)和γ-氨基丁酸(GABA)活性的应激类型。5-HT(1A)化合物在多种行为模型和临床研究中已显示出抗焦虑作用。

目的

本研究的主要目的是分析强迫游泳对三种5-HT(1A)化合物抗焦虑样作用的影响。

方法

对应激(ST)和未应激(UST)小鼠进行探索行为测试(EBT)或埋埋行为测试(BBT)。此外,使用EBT分析了5-HT(1A)化合物丁螺环酮、8-羟基二丙胺基四氢萘(8-OH-DPAT)和吲哚酯在ST和UST小鼠中剂量增加时的作用。焦虑测试后立即进行自发走动行为测试。

结果

一次强迫游泳在EBT和BBT测试的小鼠中均诱导出抗焦虑样行为。强迫游泳的这种作用被预先给予印防己毒素或WAY 100635阻断。5-HT(1A)化合物在UST动物中产生明显的抗焦虑样作用。相比之下,低剂量的8-OH-DPAT(0.01 mg/kg)、丁螺环酮(0.03 mg/kg)或吲哚酯(0.3、0.6 mg/kg)使ST小鼠在强迫游泳后观察到的抗焦虑样作用减弱。未记录到可能掩盖焦虑测试结果的走动变化。

结论

目前的数据提供了证据表明强迫游泳会诱导5-HT(1A)药物作用的变化。讨论了5-HT和/或GABA系统在这些应激诱导效应中的参与情况。

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