Belzung C, El Hage W, Moindrot N, Griebel G
EA 3248 Psychobiologie des Emotions, Faculté des Sciences et Techniques, Université Francois Rabelais, Parc de Grandmont, 37200 Tours, France.
Neuropharmacology. 2001 Sep;41(3):400-8. doi: 10.1016/s0028-3908(01)00072-7.
This article had several objectives. First it aimed at investigating the anxiogenic-like behaviors elicited by unavoidable cat exposure and/or cat odor across nine strains of mice (BALB/c, C57BL/6, C3H, CBA, DBA/2, NMRI, NZB, SJL, Swiss) in a modified version of the free-exploration test. The second objective was to investigate possible neurochemical changes following cat exposure in Swiss mice by measuring the turnover of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in several brain regions known to be involved in the modulation of emotional processes (hippocampus, hypothalamus and striatum). Finally, the third objective was to examine the effects of anxiolytic drug treatments on the anxiogenic responses elicited by a cat odor (i.e. a feces) in Swiss mice previously exposed to a cat using the free-exploration test. Results from the strain comparison showed that mice could be divided into three distinct groups: two non-reactive strains (NZB and SJL) which were relatively insensitive to predatory exposure and/or odor; five intermediate-reactive strains (Swiss, NMRI, CBA, C3H and BALB/c) which displayed clear anxiogenic-like responses only when exposed to both cat and, subsequently, to feces; and two high reactive strains (C57BL/6 and DBA/2) which showed anxiogenic-like reactions following cat exposure, regardless of the stimulus (clay or feces) present in the free-exploration cage. Neurochemical data revealed that, while brain levels of NA, DA, 5-HT in cat exposed Swiss mice were not significantly different from those of control animals, turnover rates of these monoamines were increased in the hippocampus (NA and 5-HT), hypothalamus and striatum (DA) after cat exposure. Results from pharmacological experiments indicated that repeated administration of the 5-HT reuptake inhibitor fluoxetine (5-20 mg/kg, twice a day, for 5 days) completely abolished avoidance of the cat feces in Swiss mice previously exposed to the predator. Neither acute nor repeated administration of the classical anxiolytic diazepam was able to reduce avoidance behavior of the anxiogenic stimulus in the free-exploration test. Taken together, these findings indicate that the exposure of mice to unavoidable predatory stimuli is associated with behavioral and neurochemical changes consistent with increased anxiety.
本文有几个目标。首先，旨在通过改良的自由探索试验，研究在九种品系的小鼠（BALB/c、C57BL/6、C3H、CBA、DBA/2、NMRI、NZB、SJL、瑞士小鼠）中，不可避免的猫暴露和/或猫气味引发的焦虑样行为。第二个目标是通过测量已知参与情绪过程调节的几个脑区（海马体、下丘脑和纹状体）中多巴胺（DA）、去甲肾上腺素（NA）和5-羟色胺（5-HT）的周转率，研究瑞士小鼠在接触猫后可能发生的神经化学变化。最后，第三个目标是使用自由探索试验，研究抗焦虑药物治疗对先前接触过猫的瑞士小鼠中由猫气味（即粪便）引发的焦虑反应的影响。品系比较的结果表明，小鼠可分为三个不同的组：两个无反应品系（NZB和SJL），它们对捕食性暴露和/或气味相对不敏感；五个中度反应品系（瑞士小鼠、NMRI、CBA、C3H和BALB/c），它们仅在接触猫并随后接触粪便时才表现出明显的焦虑样反应；以及两个高反应品系（C57BL/6和DBA/2），它们在接触猫后表现出焦虑样反应，无论自由探索笼中存在何种刺激（黏土或粪便）。神经化学数据显示，虽然接触猫的瑞士小鼠脑内NA、DA、5-HT水平与对照动物无显著差异，但接触猫后，这些单胺在海马体（NA和5-HT）、下丘脑和纹状体（DA）中的周转率增加。药理学实验结果表明，重复给予5-HT再摄取抑制剂氟西汀（5 - 20 mg/kg，每天两次，共5天）可完全消除先前接触过捕食者的瑞士小鼠对猫粪便的回避。在自由探索试验中，经典抗焦虑药地西泮的急性或重复给药均不能减少对焦虑刺激的回避行为。综上所述，这些发现表明，小鼠暴露于不可避免的捕食性刺激与行为和神经化学变化有关，这些变化与焦虑增加一致。
