Shachar D, Klein E, Tabak A, Finberg J P
Department of Psychiatry, Rambam Medical Center, Haifa, Israel.
Eur J Pharmacol. 1997 Aug 13;332(3):237-43. doi: 10.1016/s0014-2999(97)01084-4.
In vivo microdialysis in conscious rats was used to evaluate the effect of acute and chronic administration of fluvoxamine on extracellular levels of noradrenaline, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in the frontal cortex. A single administration of fluvoxamine (12 mg/kg i.p.) during dialysate collection caused a significant delayed decrease in 5-HIAA and a mild increase in noradrenaline with no change in HVA and DOPAC levels. Chronic administration of fluvoxamine (12 mg/kg i.p. daily for 3 weeks, last dose 24 h prior to microdialysis) or a single dose 24 h prior to microdialysis had no effect on noradrenaline, DOPAC and HVA levels in the frontal cortex; 5-HIAA levels were significantly decreased 24 h after a single dose, but increased following long term treatment. Tissue concentrations of 5-HT and 5-HIAA in the frontal cortex showed a mild (though not significant) increase in rats chronically treated with fluvoxamine. Release of noradrenaline in the frontal cortex may be enhanced initially by a 5-HT uptake inhibitor, but this effect is not seen following drug washout.
在清醒大鼠体内进行微透析，以评估急性和慢性给予氟伏沙明对额叶皮质中去甲肾上腺素、二羟基苯乙酸（DOPAC）、高香草酸（HVA）和5-羟吲哚乙酸（5-HIAA）细胞外水平的影响。在透析液采集期间单次给予氟伏沙明（12mg/kg腹腔注射）导致5-HIAA显著延迟降低，去甲肾上腺素轻度升高，而HVA和DOPAC水平无变化。慢性给予氟伏沙明（12mg/kg腹腔注射，每日1次，共3周，最后一剂在微透析前24小时给予）或在微透析前24小时给予单次剂量对额叶皮质中的去甲肾上腺素、DOPAC和HVA水平无影响；单次给药24小时后5-HIAA水平显著降低，但长期治疗后升高。在长期接受氟伏沙明治疗的大鼠中，额叶皮质中5-HT和5-HIAA的组织浓度显示出轻度（尽管不显著）升高。5-HT摄取抑制剂最初可能会增强额叶皮质中去甲肾上腺素的释放，但在药物洗脱后未观察到这种效应。
