INCREASED DOPAMINE AND NOREPINEPHRINE RELEASE IN MEDIAL PREFRONTAL CORTEX INDUCED BY ACUTE AND CHRONIC STRESS - EFFECTS OF DIAZEPAM
INCREASED DOPAMINE AND NOREPINEPHRINE RELEASE IN MEDIAL PREFRONTAL CORTEX INDUCED BY ACUTE AND CHRONIC STRESS - EFFECTS OF DIAZEPAM
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DOI：
10.1016/0306-4522(94)00331-x
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发表时间：
1995-02-01
期刊：
影响因子：
3.3
通讯作者：
ABERCROMBIE, ED
中科院分区：
文献类型：
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作者：
FINLAY, JM;ZIGMOND, MJ;ABERCROMBIE, ED
我们使用体内微透析检查了地西泮对应激诱导的内侧前额皮质细胞外多巴胺和去甲肾上腺素增加的影响。在幼稚大鼠中，急性尾压（30分钟）引起内侧前额叶皮层细胞外液中多巴胺和去甲肾上腺素浓度增加（分别增加54%和50%）。地西泮（2.5 mg/kg, ig）降低细胞外多巴胺和去甲肾上腺素的基础浓度。地西泮也能减弱应激引起的细胞外多巴胺绝对浓度的增加（+17%），但没有改变应激引起的去甲肾上腺素的增加（+41%）。然而，当考虑到药物引起的基础多巴胺和去甲肾上腺素浓度的下降时，应激引起的多巴胺高于新基线的净增加量与车辆预处理大鼠相当，而去甲肾上腺素的净增加量几乎是对照组的两倍。在先前暴露于慢性寒冷的大鼠中（在5摄氏度下3至4周），尾压再次导致内侧前额叶皮层多巴胺和去甲肾上腺素浓度增加（分别为+42%和+92%）。然而，在这些长期应激的大鼠中，地西泮不再降低细胞外液中的基础多巴胺或去甲肾上腺素，也不影响应激引起的这些儿茶酚胺浓度的增加。这些数据表明，地西泮对多巴胺和去甲肾上腺素的细胞外浓度有复杂的影响，其变化取决于大鼠在药物暴露期间是不受干扰还是有压力，以及大鼠以前的压力暴露史。此外，这些数据提出了关于儿茶酚胺在地西泮发挥其抗焦虑特性的机制中的作用的问题。
We have examined the effects of diazepam on the stress-induced increase in extracellular dopamine and norepinephrine in the medial prefrontal cortex using in vivo microdialysis. In naive rats, acute tail pressure (30 min) elicited an increase in the concentrations of dopamine and norepinephrine in extracellular fluid of medial prefrontal cortex (+54 and +50%, respectively). Diazepam (2.5 mg/kg, i.p.) decreased the basal concentration of extracellular dopamine and norepinephrine. Diazepam also attenuated the stress-evoked increase in the absolute concentrations of extracellular dopamine (+17%), but did not alter the stress-induced increase in norepinephrine (+41%). However, when the drug-induced decrease in basal dopamine and norepinephrine concentration was taken into account, the stress-induced net increase in dopamine above the new baseline was equivalent to that obtained in vehicle pretreated rats, whereas the net increase in norepinephrine was almost twice that obtained in control subjects. In rats previously exposed to chronic cold (three to four weeks at 5 degrees C), tail pressure again produced an increase in the concentrations of dopamine and norepinephrine in the medial prefrontal cortex (+42% and +92%, respectively). However, in these chronically stressed rats, diazepam no longer decreased basal dopamine or norepinephrine in extracellular fluid, nor did it affect the stress-induced increase in the concentrations of these catecholamines. These data indicate that diazepam has complex effects on the extracellular concentrations of dopamine and norepinephrine which vary depending upon whether the rat is undisturbed or stressed during the period of drug exposure as well as the rat's prior history of exposure to stress. Moreover, these data raise questions regarding the role of catecholamines in the mechanism by which diazepam exerts its anxiolytic properties.