Rutter J J, Auerbach S B
Department of Biological Sciences, Rutgers University, Piscataway, New Jersey.
J Pharmacol Exp Ther. 1993 Jun;265(3):1319-24.
The effect of acute uptake inhibition on serotonin (5-HT) in the rat central nervous system was monitored by using in vivo dialysis. Peripheral administration of the selective 5-HT uptake blocker, fluoxetine, caused a dose-dependent increase in extracellular 5-HT in both the diencephalon and the striatum. Administration of fluoxetine or sertraline, another selective 5-HT uptake inhibitor, caused a prolonged (24 hr) increase in 5-HT and decrease in 5-hydroxyindoleacetic acid. In addition, fluoxetine and sertraline attenuated the 5-HT releasing effect of fenfluramine administered 24 hr later. Local infusion of fluoxetine into the diencephalon caused an increase in 5-HT that was twice as large as the effect of peripheral injection. Peripheral fluoxetine, by enhancing extracellular 5-HT in the raphe, probably resulted in activation of somatodendritic autoreceptors and inhibition of 5-HT neuronal discharge. Thus, the increase in 5-HT in the diencephalon after peripheral fluoxetine presumably reflected a balance between decreased release and inhibition of reuptake. In support of this, after first infusing fluoxetine into the diencephalon to maximally block reuptake, peripheral injection of the uptake inhibitor caused a decrease in 5-HT.
采用体内透析法监测急性摄取抑制对大鼠中枢神经系统中5-羟色胺（5-HT）的影响。选择性5-HT摄取阻滞剂氟西汀经外周给药后，间脑和纹状体细胞外5-HT均呈剂量依赖性增加。给予氟西汀或另一种选择性5-HT摄取抑制剂舍曲林后，5-HT水平持续升高（24小时），5-羟吲哚乙酸水平降低。此外，氟西汀和舍曲林可减弱24小时后给予的芬氟拉明的5-HT释放效应。将氟西汀局部注入间脑可使5-HT增加，其增幅是外周注射效应的两倍。外周给予氟西汀后，通过提高中缝核细胞外5-HT水平，可能导致体树突自身受体激活及5-HT神经元放电受抑制。因此，外周给予氟西汀后间脑中5-HT的增加可能反映了释放减少与摄取抑制之间的平衡。与此观点相符的是，先向间脑注入氟西汀以最大程度阻断摄取后，再经外周注射摄取抑制剂会导致5-HT水平降低。
