Effect of long-term administration of antidepressant drugs on the 5-HT3 receptors that enhance the electrically evoked release of [3H]noradrenaline in the rat hippocampus.
The present study investigated the effects of various classes of antidepressant drugs (10 mg/kg per day, s.c. during 21 days) on the electrically evoked release of [3H]noradrenaline and on its modulation by the 5-HT3 receptor agonist 2-methyl-5-hydroxy-tryptamine (2-methyl-5-HT) using preloaded rat hippocampal slices. Treatments with either fluoxetine, a selective serotonin (5-HT) reuptake inhibitor, or moclobemide, a reversible type A monoamine oxidase inhibitor, increased the evoked release of [3H]noradrenaline. These two antidepressant treatments did not change, however, the magnitude of the enhancing effect of 2-methyl-5-HT on the electrically evoked release of [3H]noradrenaline. Desipramine produced a much larger increase of the electrically evoked release of [3H]noradrenaline than fluoxetine or moclobemide, and desensitized the 5-HT3 receptors that modulate this release. Trimipramine, which like desipramine has a tricyclic structure but does not block the reuptake of noradrenaline or that of 5-HT, did not increase the evoked release of [3H]noradrenaline and did not desensitize the 5-HT3 receptors that enhance the release of [3H]noradrenaline. Maprotiline, a selective noradrenaline reuptake inhibitor, did not produce the same changes as desipramine, but maprotiline inhibited noradrenaline reuptake to a lesser extent (50%) than desipramine (80%). These results suggest that the high potency noradrenaline reuptake blocker desipramine desensitizes 5-HT3 receptors modulating [3H]noradrenaline release, but that this effect is not common to all antidepressant drugs.
Mongeau
R
R
Department of Psychiatry, McGill University, Montréal, Québec, Canada.
De Montigny
C
C
Blier
P
P
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008376:Maprotiline / Q000494:pharmacology; D020912:Moclobemide; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D014299:Trimipramine / Q000494:pharmacology
D000928:Antidepressive Agents; D001549:Benzamides; D011985:Receptors, Serotonin; D005473:Fluoxetine; D008376:Maprotiline; D012701:Serotonin; D014299:Trimipramine; C045918:2-methyl-5-HT; D020912:Moclobemide; D003891:Desipramine; D009638:Norepinephrine