Finlay J M, Zigmond M J, Abercrombie E D
Department of Neuroscience, University of Pittsburgh, PA 15260, USA.
Neuroscience. 1995 Feb;64(3):619-28. doi: 10.1016/0306-4522(94)00331-x.
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.
我们使用体内微透析技术研究了地西泮对应激诱导的内侧前额叶皮质细胞外多巴胺和去甲肾上腺素增加的影响。在未处理的大鼠中，急性尾部压迫（30分钟）引起内侧前额叶皮质细胞外液中多巴胺和去甲肾上腺素浓度升高（分别升高54%和50%）。地西泮（2.5mg/kg，腹腔注射）降低了细胞外多巴胺和去甲肾上腺素的基础浓度。地西泮还减弱了应激诱发的细胞外多巴胺绝对浓度的升高（+17%），但未改变应激诱导的去甲肾上腺素升高（+41%）。然而，当考虑到药物诱导的基础多巴胺和去甲肾上腺素浓度降低时，应激诱导的多巴胺高于新基线的净增加与 vehicle 预处理大鼠的情况相当，而去甲肾上腺素的净增加几乎是对照组的两倍。在先前暴露于慢性寒冷（5摄氏度下三到四周）的大鼠中，尾部压迫再次导致内侧前额叶皮质中多巴胺和去甲肾上腺素浓度升高（分别升高42%和92%）。然而，在这些慢性应激大鼠中，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，也不影响应激诱导的这些儿茶酚胺浓度的升高。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，这取决于大鼠在药物暴露期间是否未受干扰或处于应激状态，以及大鼠先前的应激暴露史。此外，这些数据引发了关于儿茶酚胺在地西泮发挥其抗焦虑特性机制中的作用的问题。
