EFFECT OF LONG-TERM ADMINISTRATION OF ANTIDEPRESSANT DRUGS ON THE 5-HT3 RECEPTORS THAT ENHANCE THE ELECTRICALLY-EVOKED RELEASE OF [H-3] NORADRENALINE IN THE RAT HIPPOCAMPUS

The present study investigated the effects of various classes of antid epressant drugs (10 mg/kg per day, s.c. during 21 days) on the electri cally evoked release of [H-3]noradrenaline and on its modulation by th e 5-HT3 receptor agonist 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) using preloaded rat hippocampal slices. Treatments with either fluoxet ine, a selective serotonin (5-HT) reuptake inhibitor, or moclobemide, a reversible type A monoamine oxidase inhibitor, increased the evoked release of [H-3]noradrenaline. These two antidepressant treatments did not change, however, the magnitude of the enhancing effect of 2-methy l-5-HT on the electrically evoked release of [H-3]noradrenaline. Desip ramine produced a much larger increase of the electrically evoked rele ase of [H-3]noradrenaline than fluoxetine or moclobemide, and desensit ized the 5-HT3 receptors that modulate this release. Trimipramine, whi ch like desipramine has a tricyclic structure but does not block the r euptake of noradrenaline or that of 5-HT3 did not increase the evoked release of [H-3]noradrenaline and did not desensitize the 5-HT3 recept ors that enhance the release of [H-3]noradrenaline. Maprotiline, a sel ective noradrenaline reuptake inhibitor, did not produce the same chan ges as desipramine, but maprotiline inhibited noradrenaline reuptake t o a lesser extent (50%) than desipramine (80%). These results suggest that the high potency noradrenaline reuptake blocker desipramine desen sitizes 5-HT, receptors modulating [H-3]noradrenaline release, but tha t this effect is not common to all antidepressant drugs.