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

• Published in: British journal of pharmacology 2003-11, Vol.140 (6), p.1128-1136
• Main Authors: David, D J P, Bourin, M, Jego, G, Przybylski, C, Jolliet, P, Gardier, A M
• Format: Article
• Language: English
• Subjects: Animals; Antidepressants; Antidepressive Agents, Second-Generation - pharmacology; Biological and medical sciences; Citalopram - pharmacology; Cyclohexanols - pharmacology; Dose-Response Relationship, Drug; frontal cortex; Frontal Lobe - drug effects; Frontal Lobe - metabolism; Male; Medical sciences; Mice; Microdialysis; noradrenaline; Norepinephrine - secretion; Paroxetine - pharmacology; Pharmacology. Drug treatments; serotonin; Serotonin - secretion; Serotonin Uptake Inhibitors - pharmacology; Time Factors; Venlafaxine Hydrochloride
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705538

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. 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 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 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. 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. 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. British Journal of Pharmacology (2003) 140, 1128–1136. doi:10.1038/sj.bjp.0705538