Femoxetine blocks the morphine-induced increase in 5-HT metabolism, as measured by in vivo voltammetry in the nucleus raphe magnus of freely-moving rats.
Tricyclic antidepressants, when administered acutely, are known to potentiate morphine-induced antinociception. Systemic administration of morphine has been shown to increase the metabolism of serotonin (5-HT) at the level of the nucleus raphe magnus, as measured by in vivo electrochemistry, in freely-moving rats. Using a similar electrochemical detection of 5-hydroxyindole (peak "3") in the nucleus raphe magnus, the present study investigated the effect of the specific 5-HT uptake inhibitor, femoxetine, on peak 3 and on changes in the metabolism of 5-HT, induced by morphine. Acutely administered femoxetine (40 mg/kg i.p.) induced a significant decrease in peak 3 and completely abolished the effect of morphine (10 mg/kg i.p.) on the metabolism of 5-HT. These data do not support the contention that potentiation of morphine-induced analgesia, by tricyclic depressants results from an interaction between the tricyclic antidepressants and the morphine-induced increase in metabolism of 5-HT, at the level of the nucleus raphe magnus.
Puig
S
S
Unité de Recherches de Physiopharmacologie du Système Nerveux (INSERM, U 161), Paris, France.
Rivot
J P
JP
Besson
J M
JM
D000818:Animals; D004563:Electrochemistry; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010880:Piperidines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009020:Morphine; C010655:femoxetine