We have evaluated, with the use of vertical microdialysis, the effects of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) on the increase in serotonin and norepinephrine output elicited in rats prefrontal cortex by exposure to footshock stress. Exposure to footshock stress induced a marked increase in the cortical extracellular concentration of both serotonin and norepinephrine (+70% and +100%, respectively) in control rats. Long term, but not acute administration of fluvoxamine (10 mg/kg, i.p. once a days for 21 days) completely antagonized the stress induced increase in cortical serotonin extracellular concentration, while failed to modify the sensitivity of cortical noradrenergic neurons to the same stressful stimulus. Our results have shown that it is possible to independently modulate the sensitivity of cortical serotonergic neurons to stressful stimuli without altering the responsiveness of noradrenergic neurons to the same stress. Given the different role played by serotonin and norepinephrine in the modulation of the stress response, the availability of drugs able to selectively modulate the plastic response of serotonergic neurons to stress in specific brain areas might be important for the pharmacotherapy of anxiety disorders.