Lowy M T, Gault L, Yamamoto B K
Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106.
J Neurochem. 1993 Nov;61(5):1957-60. doi: 10.1111/j.1471-4159.1993.tb09839.x.
Glucocorticoids and stress have deleterious effects on hippocampal cell morphology and survival. It has been hypothesized that these effects are mediated via an excitatory amino acid mechanism. The present study was designed to evaluate the effects of acute stress on the extracellular levels of glutamate in the hippocampus and to determine if adrenalectomy modifies this response. Rats were adrenalectomized or sham-adrenalectomized and implanted with microdialysis probes in the CA3 region of the hippocampus. Three days later rats were subjected to an acute 1-h period of immobilization stress. Stress significantly increased extracellular glutamate levels in the sham-operated rats, which peaked at 20 min following the initiation of stress. Extracellular glutamate levels also increased immediately following the termination of stress. In the adrenalectomized rats there was a 30% decrease in basal extracellular concentrations of glutamate and a marked attenuation (-70%) of the stress-induced increase in extracellular glutamate levels. Extracellular concentrations of taurine were not modified by adrenalectomy and did not change in response to stress. These results suggest that glucocorticoid-induced elevations in extracellular glutamate concentrations may contribute to the deleterious effects of stress on hippocampal neurons.
糖皮质激素和应激对海马体细胞形态及存活具有有害影响。据推测，这些影响是通过兴奋性氨基酸机制介导的。本研究旨在评估急性应激对海马体中谷氨酸细胞外水平的影响，并确定肾上腺切除术是否会改变这种反应。将大鼠进行肾上腺切除或假肾上腺切除，并在海马体CA3区植入微透析探针。三天后，对大鼠施加1小时的急性固定应激。应激显著增加了假手术大鼠的细胞外谷氨酸水平，在应激开始后20分钟达到峰值。应激终止后，细胞外谷氨酸水平也立即升高。在肾上腺切除的大鼠中，谷氨酸的基础细胞外浓度降低了30%，应激诱导的细胞外谷氨酸水平升高显著减弱（-70%）。肾上腺切除术未改变牛磺酸的细胞外浓度，且牛磺酸浓度对应激无反应。这些结果表明，糖皮质激素诱导的细胞外谷氨酸浓度升高可能导致应激对海马体神经元的有害影响。
