Kirby L G, Kreiss D S, Singh A, Lucki I
Department of Psychiatry, University of Pennsylvania Philadelphia 19104-2649, USA.
Synapse. 1995 Jun;20(2):99-105. doi: 10.1002/syn.890200202.
This study examined the relationship between the magnitude of tissue serotonin (5-HT) depletion produced by treatment with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and basal and fenfluramine-induced 5-HT release in the striatum. Separate groups of rats were treated with either vehicle or 5,7-DHT (100 micrograms: 76% striatal 5-HT depletion; or 200 micrograms: 93% striatal 5-HT depletion). Four weeks after treatment, 5-HT release was measured in the ventral striatum using in vivo microdialysis in animals anesthetized with chloral hydrate. Basal 5-HT levels were not significantly altered in any lesion group, whereas basal 5-hydroxyindoleacetic acid levels were dose-dependently reduced by 5,7-DHT. In contrast, the increase of 5-HT release produced by fenfluramine treatment (10 mg/kg) was diminished significantly after 5-HT neuronal destruction in correlation with the reduction of striatal tissue 5-HT content. Fractional 5-HT efflux, a measure of the 5-HT release from surviving striatal nerve terminals, was also significantly elevated when tissue depletion of 5-HT exceeded 95%. This study suggests that compensatory mechanisms may enable surviving 5-HT terminals to maintain basal 5-HT levels in the striatum with as little as 5% of the terminals remaining, but those mechanisms are not sufficient to allow the damaged system to respond to a pharmacological challenge.
本研究考察了用神经毒素5,7 - 二羟基色胺（5,7 - DHT）处理所导致的组织中血清素（5 - HT）耗竭程度与纹状体中基础及芬氟拉明诱导的5 - HT释放之间的关系。将大鼠分成不同组，分别给予赋形剂或5,7 - DHT（100微克：纹状体5 - HT耗竭76%；或200微克：纹状体5 - HT耗竭93%）。处理四周后，在用水合氯醛麻醉的动物中，通过体内微透析法测量腹侧纹状体中的5 - HT释放。在任何损伤组中，基础5 - HT水平均未发生显著改变，而基础5 - 羟吲哚乙酸水平则随5,7 - DHT剂量依赖性降低。相反，在5 - HT神经元破坏后，芬氟拉明处理（10毫克/千克）所引起的5 - HT释放增加与纹状体组织5 - HT含量的降低相关，显著减少。当5 - HT的组织耗竭超过95%时，作为衡量存活纹状体神经末梢5 - HT释放指标的5 - HT分数流出量也显著升高。本研究表明，代偿机制可能使仅5%的存活末梢就能维持纹状体中的基础5 - HT水平，但这些机制不足以让受损系统应对药理学刺激。
