CHARACTERIZATION OF HIPPOCAMPAL NOREPINEPHRINE RELEASE AS MEASURED BY MICRODIALYSIS PERFUSION - PHARMACOLOGICAL AND BEHAVIORAL-STUDIES
CHARACTERIZATION OF HIPPOCAMPAL NOREPINEPHRINE RELEASE AS MEASURED BY MICRODIALYSIS PERFUSION - PHARMACOLOGICAL AND BEHAVIORAL-STUDIES
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DOI：
10.1016/0306-4522(88)90192-3
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发表时间：
1988-12-01
期刊：
影响因子：
3.3
通讯作者：
ZIGMOND, MJ
中科院分区：
文献类型：
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作者：
ABERCROMBIE, ED;KELLER, RW;ZIGMOND, MJ
采用微透析灌流法研究自由活动大鼠海马内源性去甲肾上腺素的释放。使用环型透析探针，在15分钟部分中收集的去甲肾上腺素的基础量平均为12 pg/25 μ l。校正回收率（21%）后，静息条件下海马细胞外液中去甲肾上腺素的浓度估计约为14 nM。α 2肾上腺素受体拮抗剂育亨宾（5.0 mg/kg i. p.）增加去甲肾上腺素外排至基础水平的230%。可乐定（0.3 mg/kg i. p.），一种α 2肾上腺素受体激动剂，将去甲肾上腺素流出量降低至基线的565。向灌注液中加入再摄取阻断剂地昔帕明（1.0 μ M）对去甲肾上腺素流出没有显著影响。然而，将灌注液的K+浓度增加至30 mM使去甲肾上腺素流出量增加至基线的196%，并且通过向灌注液中加入地昔帕明（基线的364%），该效果增加近两倍。束缚应激和间歇性尾休克使去甲肾上腺素流出量分别增加至基线的213%和234%。结果表明，微透析是一种有用的方法来研究去甲肾上腺素释放在海马，他们允许得出几个结论。首先，系统给予α 2肾上腺素受体药物获得的数据强调了这样一个事实，即存在多种可能影响细胞外液中递质水平的调节机制。第二，海马组织中细胞外去甲肾上腺素与细胞内去甲肾上腺素的比例远高于纹状体中多巴胺的比例。再加上去甲肾上腺素摄取阻滞的小作用，这表明神经末梢密度是决定细胞外液中儿茶酚胺浓度的重要因素。最后，所观察到的压力引起的增加去甲肾上腺素流出支持蓝斑去甲肾上腺素能系统在压力条件下发挥重要的中枢影响的假设。
The release of endogenous norepinephrine in hippocampus was studied in freely moving rats with microdialysis perfusion. Using a loop-style dialysis probe, the basal amount of norepinephrine collected in 15-min fractions averaged 12 pg/25 .mu.l. Correcting for recovery (21%), the concentration of norepinephrine in the extracellular fluid of hippocampus under resting conditions was estimated to be approximately 14 nM. The alpha2 adrenoceptor, antagonist yohimbine (5.0 mg/kg i.p.) increased norepinephrine efflux to 230% of basal levels. Clonidine (0.3 mg/kg i.p.), an alpha2 adrenoceptor agonist, decreased norepinephrine efflux to 565 of baseline. Addition of the reuptake blocker desipramine (1.0 .mu.M) to the perfusate had no significant effect on norepinephrine efflux. However, increasing the K+ concentration of the perfusate to 30 mM increased norepinephrine efflux to 196% of baseline, and this effect was increased nearly two-fold by the addition of desipramine to the perfusate (364% of baseline). Restraint stress and intermittent tailshock increased norepinephrine efflux to 213% and 234% of baseline, respectively. The results suggest that microdialysis is a useful way to study norepinephrine release in hippocampus and they permit several conclusions to be drawn. First, the data obtained with systemic adminstration of alpha2 adrenoceptor drugs emphasize the fact that a variety of regulatory mechanisms exist that may affect transmitter levels in the extracellular fluid. Second, the ratio of extracellular to intracellular norepinephrine in hippocampal tissue is considerably higher than that reported for dopamine in striatum. Coupled with the small effect of norepinephrine uptake blockade, this suggests that nerve terminal density is an important factor in determining the concentration of catecholamines in the extracellular fluid. Finally, the observed stress-induced increase in norepinephrine efflux supports the hypothesis that the locus coeruleus noradrenergic system exerts an important central influence during stressful conditions.