Exposure to novelty and forced swimming evoke stressor-dependent changes in extracellular GABA in the rat hippocampus
Exposure to novelty and forced swimming evoke stressor-dependent changes in extracellular GABA in the rat hippocampus
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DOI：
10.1016/j.neuroscience.2007.06.030
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发表时间：
2007-09-07
期刊：
影响因子：
3.3
通讯作者：
Linthorst, A. C. E.
中科院分区：
文献类型：
--
作者：
de Groote, L.;Linthorst, A. C. E.
在海马区，一个在应激反应中至关重要的大脑结构，GABA不仅通过突触抑制来控制神经元的活动，而且通过刺激突触外的GABA受体来控制紧张性抑制。细胞外GABA水平可能代表紧张性抑制的一个主要决定因素，因此，令人惊讶的是，它对压力的反应几乎没有被研究过。为了阐明海马区细胞外GABA水平是否在急性应激反应中发生变化，我们在大鼠体内进行了一项微透析研究。我们发现，透析液中的GABA水平对再摄取抑制、K+、河豚毒素和巴氯芬浓度升高等神经药理操作有反应，表明海马胞外GABA的很大一部分依赖于神经元的释放，而GABA的再摄取在决定这种神经递质的胞外水平中起着作用。接下来，大鼠被暴露在一个新的笼子里或被迫在25摄氏度的水中游泳。有趣的是，这两个压力源导致了相反的效果。新鲜感导致GABA迅速增加(基线的120%)，而强迫游泳导致GABA显著下降(基线的70%)。为了区分强迫游泳的心理和生理方面(即对体温的影响)，另一组动物被迫在35摄氏度的温度下游泳。像新鲜感一样，这种应激源导致海马区GABA增加，表明心理应激的刺激作用。促肾上腺皮质激素释放因子受体拮抗剂D-Phe-CRF12-41不能阻止这种新颖性的作用。这些结果首次证明了海马胞外GABA的应激性变化；这一观察结果可能对GABA能紧张性抑制海马神经元具有特别重要的意义。(C)2007年IBRO。爱思唯尔有限公司出版。保留所有权利。
In the hippocampus, a brain structure critically important in the stress response, GABA controls neuronal activity not only via synaptic inhibition, but also via tonic inhibition through stimulation of extrasynaptic GABA receptors. The extracellular level of GABA may represent a major determinant for tonic inhibition and, therefore, it is surprising that its responsiveness to stress has hardly been investigated. To clarify whether hippocampal extracellular GABA levels change in response to acute stress, we conducted an in vivo microdialysis study in rats. We found that dialysate GABA levels respond to various neuropharmacological manipulations such as reuptake inhibition, elevated concentrations of K+, tetrodotoxin and baclofen, indicating that a large proportion of hippocampal extracellular GABA depends on neuronal release and that GABA re-uptake plays a role in determining the extracellular levels of this neurotransmitter. Next, rats were exposed to a novel cage or to forced swimming in 25 degrees C water. Interestingly, these two stressors resulted in opposite effects. Novelty caused a fast increase in GABA (120% of baseline), whereas forced swimming resulted in a profound decrease (70% of baseline). To discriminate between the psychological and physical aspects (i.e. the effects on body temperature) of forced swimming, another group of animals was forced to swim at 35 degrees C. This stressor, like novelty, caused an increase in hippocampal GABA, suggesting a stimulatory effect of psychological stress. The effects of novelty could not be blocked by the corticotropin-releasing factor receptor antagonist D-Phe-CRF12-41. These results are the first to demonstrate stressor-dependent changes in hippocampal extracellular GABA; an observation which may be of particular significance for GABAergic tonic inhibition of hippocampal neurons. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.