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 effec t of acute and chronic administration of fluvoxamine on extracellular levels of noradrenaline, dihydroxyphenylacetic acid (DOPAC), homovanil lic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in the fronta l cortex. A single administration of fluvoxamine (12 mg/kg i.p.) durin g 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 decreas ed 24 h after a single dose, but increased following long term treatme nt. Tissue concentrations of 5-HT and 5-HIAA in the frontal cortex sho wed a mild (though not significant) increase in rats chronically treat ed with fluvoxamine. Release of noradrenaline in the frontal cortex ma y be enhanced initially by a 5-HT uptake inhibitor, but this effect is not seen following drug washout. (C) 1997 Elsevier Science B.V.