Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, 26/28 Krakowskie Przedmieście, Warsaw, 00-927, Poland.
Behav Brain Res. 2013 Sep 15;253:337-45. doi: 10.1016/j.bbr.2013.07.042. Epub 2013 Jul 31.
This study assessed the mechanisms underlying the behavioral differences between high- (HR) and low-anxiety (LR) rats selected for their behavior in the contextual fear test (i.e., the duration of the freezing response was used as a discriminating variable). Rats were subjected to chronic restraint stress (21 days, 3h daily). We found that in the HR group, chronic restraint stress decreased rat activity in the Porsolt test and reduced the concentration of corticosterone in the prefrontal cortex. The behavioral changes were accompanied by a lower expression of alpha-2 GABA-A receptor subunits in the secondary motor cortex (M2 area) and in the dentate gyrus of the hippocampus (DG) compared to LR restraint animals. Moreover, restraint stress increased the density of alpha-2 GABA-A subunits in the basolateral amygdala (BLA) in HR rats and decreased the expression of these subunits in the DG and M2 areas compared to the HR control group. The present results suggest that, in HR rats exposed to chronic restraint stress, the function of hippocampal and cortical GABAergic neurotransmission is attenuated and that this effect could have important influences on the functioning of the hypothalamic-pituitary-adrenal axis and on depressive symptoms.
本研究评估了在情境恐惧测试中选择的高焦虑（HR）和低焦虑（LR）大鼠之间行为差异的潜在机制（即，冻结反应的持续时间用作区分变量）。大鼠接受慢性束缚应激（21 天，每天 3 小时）。我们发现，在 HR 组中，慢性束缚应激降低了 Porsolt 测试中大鼠的活动，并降低了前额叶皮质中的皮质酮浓度。与 LR 束缚动物相比，行为变化伴随着次级运动皮层（M2 区）和海马齿状回（DG）中 alpha-2 GABA-A 受体亚基的表达降低。此外，与 HR 对照组相比，慢性束缚应激增加了 HR 大鼠基底外侧杏仁核（BLA）中 alpha-2 GABA-A 亚基的密度，并降低了 DG 和 M2 区这些亚基的表达。目前的结果表明，在暴露于慢性束缚应激的 HR 大鼠中，海马和皮质 GABA 能神经传递的功能减弱，这可能对下丘脑-垂体-肾上腺轴的功能和抑郁症状产生重要影响。
