Effect of single and repeated administration of fluvoxamine on noradrenaline release in rat brain

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.