In vivo electrochemical evidence that the tricyclic antidepressant femoxetine potentiates the morphine-induced increase in 5-HT metabolism in the medullary dorsal horn of freely moving rats.
Acute administration of tricyclic antidepressants (TCAs) is known to potentiate morphine antinociception. At the medullary dorsal horn (MDH) level systemic morphine has been shown to increase serotonin (5-HT) metabolism as measured by in vivo electrochemistry in freely moving rats. Using similar electrochemical detection of 5-hydroxyindole (peak '3') within the MDH, the present study investigated the effect of the specific 5-HT uptake inhibitor femoxetine on peak 3 and the effects of this TCA on changes in 5-HT metabolism induced by morphine. Acutely administered femoxetine (40 mg/kg i.p.) (i) induced a small but significant increase in peak 3 and (ii) strongly potentiated the effect of morphine (10 mg/kg i.p.) on 5-HT metabolism, this potentiation being opiate specific since simultaneous injection of naloxone (1 mg/kg i.p.) abolished the effect of morphine. These findings provide an in vivo neurochemical basis for the potentiation of morphine antinociception by TCAs. They further emphasize the importance of 5-HT bulbospinal descending pathways in morphine antinociception.
Unité de Recherches de Physiopharmacologie du Système Nerveux, INSERM U 161, Paris, France.
S
S
Puig
J P
JP
Rivot
J M
JM
Besson
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001692:Biological Transport; D004357:Drug Synergism; D004563:Electrochemistry / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity; D009270:Naloxone / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D009270:Naloxone; D009020:Morphine; C010655:femoxetine