Bagley J, Moghaddam B
Department of Psychiatry, Yale University School of Medicine, VA Medical Center 116A/2, West Haven, CT 06516, USA.
Neuroscience. 1997 Mar;77(1):65-73. doi: 10.1016/s0306-4522(96)00435-6.
Acute stress has been associated with activation of glutamate efflux in forebrain structures. The present study sought to characterize the extracellular dynamics of glutamate in response to acute and repeated stress in the prefrontal cortex and hippocampus in rats. One-minute sampling of extracellular glutamate levels was performed during repeated tail-pinch stress. Animals were stressed three times, beginning at approximately 10.30 a.m. and continuing at 2.5-h intervals. In the prefrontal cortex, the initial 10-min tail pinch produced a robust increase in extracellular levels of glutamate. This increase was apparent immediately (i.e. 1 min) after the start of the stress procedure. The second tail pinch produced a smaller increase in glutamate levels while the third tail pinch did not significantly increase these levels. In the hippocampus, the initial stress response was smaller in magnitude than that observed in the prefrontal cortex. Furthermore, responses to subsequent tail pinches were similar to that seen following the first tail pinch. Treatment with diazepam (3 mg/kg/i.p.) 30 min before the first stress session abolished the stress response in the prefrontal cortex and hippocampus. However, in the prefrontal cortex, the second tail pinch (performed approximately 3 h after diazepam administration) produced a robust increase in glutamate efflux. In contrast, in the hippocampus of diazepam-treated rats, the second tail pinch produced a small delayed response. Pretreatment with saline resulted in non-significant responses to all three tail pinches in the prefrontal cortex. The present study suggests that: (i) stress produces a rapid increase in glutamate efflux in the prefrontal cortex and hippocampus, (ii) repeated stress reveals tolerance in the glutamatergic response in the prefrontal cortex, (iii) saline and diazepam pretreatment reduce the stress-induced efflux of glutamate in the prefrontal cortex, and (iv) exposure to diazepam may prevent the prefrontal cortex from adapting its response to the subsequent stressor. These finding are consistent with the role of the prefrontal cortex as a region which may regulate reactions to aversive stimuli.
急性应激与前脑结构中谷氨酸外流的激活有关。本研究旨在描述大鼠前额叶皮层和海马体中谷氨酸在急性和反复应激反应中的细胞外动力学特征。在反复尾部夹捏应激期间，对细胞外谷氨酸水平进行1分钟的采样。动物接受三次应激，从上午10:30左右开始，每隔2.5小时进行一次。在前额叶皮层，最初10分钟的尾部夹捏使细胞外谷氨酸水平显著升高。这种升高在应激程序开始后立即（即1分钟）就很明显。第二次尾部夹捏使谷氨酸水平的升高幅度较小，而第三次尾部夹捏并未使这些水平显著升高。在海马体中，最初的应激反应幅度小于在前额叶皮层中观察到的反应。此外，对随后尾部夹捏的反应与第一次尾部夹捏后的反应相似。在第一次应激 session 前30分钟腹腔注射地西泮（3 mg/kg）可消除前额叶皮层和海马体中的应激反应。然而，在前额叶皮层中，第二次尾部夹捏（在地西泮给药后约3小时进行）使谷氨酸外流显著增加。相比之下，在地西泮处理的大鼠海马体中，第二次尾部夹捏产生了一个小的延迟反应。生理盐水预处理导致前额叶皮层对所有三次尾部夹捏的反应均不显著。本研究表明：（i）应激使前额叶皮层和海马体中的谷氨酸外流迅速增加，（ii）反复应激显示前额叶皮层谷氨酸能反应出现耐受性，（iii）生理盐水和地西泮预处理可降低应激诱导的前额叶皮层谷氨酸外流，（iv）接触地西泮可能会阻止前额叶皮层适应对随后应激源的反应。这些发现与前额叶皮层作为一个可能调节对厌恶刺激反应的区域的作用一致。
