Effects of acute treatment with paroxetine, citalopram and venlafaxine in vivo on noradrenaline and serotonin outflow: a microdialysis study in Swiss mice

1. This study investigated whether a single administration of a range of doses (1, 4 and 8 mg kg-1, i.p.) of paroxetine, citalopram or venlafaxine may simultaneously increase extracellular levels of 5-HT ([5-HT]ext) and noradrenaline ([NA]ext) by using in vivo microdialysis in the frontal cortex (FCx) of awake, freely moving Swiss mice. 2. In vivo, paroxetine induced similar increases in cortical [5-HT]ext at the three doses tested, and induced a statistically significant increase in cortical [NA]ext at 4 and 8 mg x kg-1. Citalopram increased neither [5-HT]ext nor [NA]ext at the lowest dose, but increased both neurotransmitter levels at 4 and 8 mg x kg-1. At these doses, citalopram induced greater increases in cortical [5-HT]ext than in [NA]ext. Venlafaxine increased [5-HT]ext and [NA]ext to about 400 and 140% of the respective basal values at 8 mg kg-1. 3. Citalopram and paroxetine have the highest potency to increase cortical [5-HT]ext and [NA]ext, respectively. In addition, the rank of order of efficacy of these antidepressant drugs to increase [5-HT]ext in vivo in the FCx of mice was as follows: venlafaxine>citalopram>paroxetine, while the efficacy to increase cortical [NA]ext in mice of paroxetine and citalopram is similar, and greater than that of venlafaxine. 4. In conclusion, extracellular levels of cortical [NA]ext increase with the highest doses of the very selective SSRI citalopram, as well as with the very potent SSRI paroxetine. Surprisingly, the SNRI venlafaxine increased cortical [5-HT]ext to a greater extent rather than [NA]ext in the range of doses studied in mice.