Campbell I C, McKernan R M
Brain Res. 1986 May 7;372(2):253-9. doi: 10.1016/0006-8993(86)91132-7.
Synaptosomes (P2) were prepared from cerebral cortices of control rats and from those which had received clorgyline (1 mg/kg/day for 21-28 days) or desipramine (10 mg/kg/day for 21-28 days). Following incubation with [3H]noradrenaline (500 nM/15 min, 37 degrees C), aliquots of the synaptosomes were gently filtered onto Whatman GF/A filters and superfused with Krebs buffer (pH 7.5, 37 degrees C) for a maximum period of 2 h. During this time, the basal efflux of tritiated materials (approximately 75% noradrenaline) together with K+-evoked release of the amine and metabolites, were measured. Chronic antidepressant drug regimens increased the K+-stimulated release, but its attenuation by clonidine was not altered. Thus, chronic antidepressant drug regimens do not apparently alter presynaptic alpha 2-adrenoceptors. These results suggest that the reported antidepressant drug induced decreases in [3H]clonidine binding, occur on sites which are postsynaptic to noradrenergic neurones. Following the chronic antidepressant drug regimens, the sensitivity of the [3H]noradrenaline release process to Ca2+ is significantly increased. This change may explain the enhanced K+-evoked release which follows the antidepressant drug regimens. It is proposed that this increased sensitivity of the [3H]noradrenaline release process may be an adaptation to the decrease in neuronal firing which have been reported following antidepressant drug treatments.
突触体（P2）取自对照大鼠的大脑皮层以及接受过氯吉兰（1毫克/千克/天，持续21 - 28天）或地昔帕明（10毫克/千克/天，持续21 - 28天）处理的大鼠的大脑皮层。与[3H]去甲肾上腺素（500纳摩尔/15分钟，37摄氏度）孵育后，将突触体的等分试样轻轻过滤到沃特曼GF/A滤膜上，并用克雷布斯缓冲液（pH 7.5，37摄氏度）进行长达2小时的灌流。在此期间，测量氚标记物质的基础流出量（约75%为去甲肾上腺素）以及钾离子诱发的胺和代谢产物的释放量。慢性抗抑郁药物治疗方案增加了钾离子刺激的释放，但可乐定对其的抑制作用未改变。因此，慢性抗抑郁药物治疗方案显然不会改变突触前α2 - 肾上腺素能受体。这些结果表明，所报道的抗抑郁药物引起的[3H]可乐定结合减少，发生在去甲肾上腺素能神经元的突触后位点。在慢性抗抑郁药物治疗方案之后，[3H]去甲肾上腺素释放过程对钙离子的敏感性显著增加。这种变化可能解释了抗抑郁药物治疗方案后钾离子诱发的释放增强的现象。有人提出，[3H]去甲肾上腺素释放过程这种增加的敏感性可能是对在抗抑郁药物治疗后所报道的神经元放电减少的一种适应。
