Yadid G, Pacak K, Kopin I J, Goldstein D S
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
J Pharmacol Exp Ther. 1994 Sep;270(3):1158-65.
Serotonin (5-HT) and dopamine (DA) are established neurotransmitters in the brain. This study examined whether, in conscious, free-moving rats, increased concentrations of endogenous 5-HT in extracellular fluid of the corpus striatum affect local release of endogenous DA. Administration of the 5-HT reuptake blocker alaproclate via a microdialysis probe increased striatal dialysate levels of DA and its metabolites dihydroxyphenylacetic acid and homovanillic acid as well as levels of 5-HT and the 5-HT metabolite 5-hydroxyindoleacetic acid. Whereas DA reuptake blockade with GBR-12909 did not prevent these effects of alaproclate, serotonergic ablation by i.c.v. administration of 5,7-dihydroxytryptamine markedly decreased basal levels of 5-HT and 5-hydroxyindoleacetic acid and abolished the effects of alaproclate on dialysate levels of DA, 5-HT and their metabolites. The results are consistent with a stimulatory action of endogenous 5-HT on striatal DA release in conscious animals.
血清素(5-羟色胺,5-HT)和多巴胺(DA)是已确定的脑内神经递质。本研究检测了在清醒、自由活动的大鼠中,纹状体细胞外液中内源性5-HT浓度的升高是否会影响内源性DA的局部释放。通过微透析探针给予5-HT再摄取阻滞剂阿扑氯丙嗪,可提高纹状体透析液中DA及其代谢物二羟基苯乙酸和高香草酸的水平,以及5-HT和5-HT代谢物5-羟吲哚乙酸的水平。虽然用GBR-12909阻断DA再摄取并不能阻止阿扑氯丙嗪的这些作用,但通过脑室内注射5,7-二羟基色胺进行的5-羟色胺能神经损毁显著降低了5-HT和5-羟吲哚乙酸的基础水平,并消除了阿扑氯丙嗪对透析液中DA、5-HT及其代谢物水平的影响。这些结果与内源性5-HT对清醒动物纹状体DA释放具有刺激作用一致。