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慢性可变应激抑郁模型中急性应激诱导的生化和行为变化:阿米替林的作用

Biochemical and behaviour changes induced by acute stress in a chronic variate stress model of depression: the effect of amitriptyline.

作者信息

Ferretti C, Blengio M, Gamalero S R, Ghi P

机构信息

Istituto di Farmacologia e Terapia Sperimentale, Torino, Italy.

出版信息

Eur J Pharmacol. 1995 Jun 23;280(1):19-26. doi: 10.1016/0014-2999(95)00172-h.

DOI:10.1016/0014-2999(95)00172-h
PMID:7498250
Abstract

This paper examines the biochemical and behaviour changes induced by an acute stress (five 10-s, 1-mA foot-shocks) in three groups of rats: (1) never stressed, (2) subjected to chronic variate stress for 20 days, (3) subjected to the same chronic stress and treated with 5 mg/kg per day amitriptyline. After 15 min, acute stress led to a marked reduction in cortical beta-adrenoceptor and 5-HT2 receptor density, whereas the density of the 5-HT1A receptors was unchanged. Chronic stress also increased beta-adrenoceptor and 5-HT2 receptor density and had no effect on 5-HT1A. Acute stress diminished the density of beta-adrenoceptors in chronically stressed animals, but did not alter that of the two 5-HT populations. Amitriptyline alone reduced beta-adrenoceptor and 5-HT2 receptor densities only. Acute stress applied to animals treated with amitriptyline reduced 5-HT1A receptors, and caused a further beta-adrenoceptor decrease, but had no further effect on the 5-HT2 receptors. On behaviour, chronic stress diminished reactivity to the acute stress. This reduction was fully abolished by amitriptyline. An open-field study showed that acute stress reduced motor activity, increased latency times and diminished rearing in the controls, whereas chronic stress reduced motor activity only. No significant changes in behaviour were induced by the acute stress in animals subjected to chronic stress. The combination of chronic stress with amitriptyline was accompanied by a diminution of exploratory activity that persisted after the acute stress.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

本文研究了三组大鼠在急性应激(五次10秒、1毫安的足部电击)下引起的生化和行为变化:(1)从未受过应激的大鼠;(2)遭受20天慢性可变应激的大鼠;(3)遭受相同慢性应激并每天接受5毫克/千克阿米替林治疗的大鼠。15分钟后,急性应激导致皮质β-肾上腺素能受体和5-HT2受体密度显著降低,而5-HT1A受体密度未发生变化。慢性应激也增加了β-肾上腺素能受体和5-HT2受体密度,对5-HT1A受体无影响。急性应激使慢性应激动物的β-肾上腺素能受体密度降低,但未改变两种5-HT受体的密度。单独使用阿米替林仅降低了β-肾上腺素能受体和5-HT2受体密度。对接受阿米替林治疗的动物施加急性应激会降低5-HT1A受体,并导致β-肾上腺素能受体进一步减少,但对5-HT2受体没有进一步影响。在行为方面,慢性应激降低了对急性应激的反应性。这种降低被阿米替林完全消除。一项旷场实验表明,急性应激降低了对照组的运动活动、增加了潜伏期并减少了竖毛行为,而慢性应激仅降低了运动活动。慢性应激动物受到急性应激后行为无显著变化。慢性应激与阿米替林联合使用会导致探索活动减少,且在急性应激后仍持续存在。(摘要截断于250字)

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