Antagonism of the stress-induced increase in cortical norepinephrine output by the selective norepinephrine reuptake inhibitor reboxetine.

We have previously shown that long-term treatment of rats with antidepressant drugs that affect the activity of noradrenergic and serotonergic neurons by different mechanisms, inhibits the increase in cortical norepinephrine output induced by stress. With the use of microdialysis, we have now evaluated the effects of reboxetine, an antidepressant drug that selectively inhibits norepinephrine reuptake, on the increase in cortical norepinephrine output elicited in rats by exposure to foot-shock stress or by the acute administration of N-methyl-beta-carboline-3-carboxamide (FG 7142) (20 mg/kg, i.p.). Foot-shock stress and FG 7142 each induced a marked increase in the cortical extracellular concentration of norepinephrine (+200 and +90%, respectively) in control rats. Long-term treatment with reboxetine (10 mg/kg, i.p., once a day for 21 days) reduced the effect of foot-shock stress and completely antagonized the effect of FG 7142 on cortical norepinephrine output. Our results suggest that changes in the activity of noradrenergic neurons in the cortex might be relevant to the anxiolytic and antidepressant effects of reboxetine.