AN ANALYSIS OF THE EFFECTS OF ACUTE AND CHRONIC FLUOXETINE ON EXTRACELLULAR NOREPINEPHRINE IN THE RAT HIPPOCAMPUS DURING STRESS

The locus coeruleus (LC) noradrenergic system is activated by a range of arousing and stressful stimuli. The serotonergic inputs to this str ucture have been shown to attenuate LC activation under some condition s. The present study examined the effect of fluoxetine, a selective se rotonin reuptake inhibitor (SSRI) known to be a clinically effective a ntidepressant, on basal and stress-induced norepinephrine (NE) release . Basal and stress-induced NE efflux in the rat hippocampus were asses sed using in vivo microdialysis techniques. The effect of a 30 minute tailpinch stressor on extracellular concentration of NE was compared i n rats treated with fluoxetine either once prior to tailpinch or twice daily for 14 days and, respectively, in unhandled controls and vehicl e-treated control animals. A single fluoxetine injection prior to tail pinch did not significantly alter the tailpinch-induced increase of ex tracellular NE as compared to naive controls. However, there was an en hanced NE response to tailpinch in chronic fluoxetine versus chronic v ehicle-treated control rats. Thus, acute blockade of 5-HT uptake by fl uoxetine does not affect NE release in response to tailpinch stress. C hronic fluoxetine administration, however, results in a potentiated ev oked response of the LC-NE system. One action of chronic fluoxetine, w hich may relate to therapeutic efficacy, is an increase in responsivit y of LC neurons. (C) 1997 American College of Neuropsychopharmacology.