Jackson D, Abercrombie E D
Department of Psychiatry, University of California, San Diego, La Jolla.
J Neurochem. 1992 Mar;58(3):890-7. doi: 10.1111/j.1471-4159.1992.tb09340.x.
Destruction of nigrostriatal dopamine (DA) neurons with 6-hydroxydopamine (6-OHDA) early in development results in hyperinnervation of striatum by the serotonergic afferents deriving from the dorsal raphe nucleus. We have used in vivo microdialysis to investigate the degree to which serotonergic neurotransmission in striatum is altered by this increase in the density of serotonin (5-HT) terminals. The effects of several manipulations known to influence 5-HT function on extracellular 5-HT and 5-hydroxyindoleacetic acid in striatum were compared in adult rats treated neonatally with 6-OHDA and in intact adult rats. Basal levels of 5-HT in extracellular fluid (ECF) of striatum were similar in neonatally DA-depleted rats and in intact rats. Perfusion with the 5-HT reuptake blocker, fluoxetine (100 microM), increased 5-HT in striatal ECF of neonatally DA-depleted rats to levels that were threefold greater than those achieved in intact rats. Likewise, K(+)-depolarization of the 5-HT terminals (100 mM in perfusate) or systemic administration of the 5-HT releaser, (+/-)-fenfluramine (10 mg/kg i.p.), increased the concentration of 5-HT in striatal ECF of neonatally DA-depleted rats to levels approximately threefold greater than those observed in striatum of intact rats. These findings indicate that the 5-HT hyperinnervation of striatum that takes place in rats depleted of DA at infancy is associated with an increased capacity for neurotransmitter release in this system. Concomitant increased in high-affinity 5-HT uptake may prevent the occurrence of any measurable changes in the resting concentration of 5-HT in striatal ECF.
在发育早期用6-羟基多巴胺（6-OHDA）破坏黑质纹状体多巴胺（DA）神经元，会导致来自背侧中缝核的5-羟色胺能传入纤维对纹状体的过度支配。我们利用体内微透析技术来研究纹状体中5-羟色胺能神经传递因5-羟色胺（5-HT）终末密度增加而改变的程度。在新生期用6-OHDA处理的成年大鼠和完整成年大鼠中，比较了几种已知影响5-HT功能的操作对纹状体细胞外5-HT和5-羟基吲哚乙酸的作用。新生期DA缺失大鼠和完整大鼠纹状体细胞外液（ECF）中5-HT的基础水平相似。用5-HT再摄取阻断剂氟西汀（100 microM）灌注，使新生期DA缺失大鼠纹状体ECF中的5-HT增加到比完整大鼠中达到的水平高三倍的水平。同样，5-HT终末的K（+）去极化（灌注液中100 mM）或全身给予5-HT释放剂（+/-）芬氟拉明（10 mg/kg腹腔注射），使新生期DA缺失大鼠纹状体ECF中5-HT的浓度增加到比完整大鼠纹状体中观察到的水平大约高三倍的水平。这些发现表明，在幼年时DA缺失的大鼠中发生的纹状体5-HT过度支配与该系统中神经递质释放能力的增加有关。高亲和力5-HT摄取的同时增加可能会阻止纹状体ECF中5-HT静息浓度出现任何可测量变化的发生。
