In the rat forced swimming test, NA-system mediated interactions may prevent the 5-HT properties of some subacute antidepressant treatments being expressed.
In the rat forced swimming test (FST), reuptake inhibitors selective of either serotonin (5-HT) or noradrenaline (NA) decrease immobility duration, and increase, respectively, swimming and climbing behaviour. In this study, an almost total 6-OHDA-induced NA-depletion prevented the behavioural effects of desipramine, but not fluoxetine. Interestingly, the serotonin/noradrenaline-reuptake-inhibitor milnacipran, as well as a (desipramine+fluoxetine) combination, could produce both swimming and climbing behaviour in NA-lesioned rats, but not in non-lesioned. The new antidepressant mirtazapine, which enhances both 5-HT and NA transmissions, supposedly through the antagonizing of alpha(2)-adrenoreceptors, dose-dependently reduced immobility and increased climbing behaviour. Interestingly, a (mirtazapine+fluoxetine) combination treatment resulted in additive anti-immobility effects and in the summation of fluoxetine-induced swimming with mirtazapine-induced climbing. Taken together, these data suggest that the NA system mediates presynaptic inhibiting interactions on the 5-HT system, that may involve alpha(2)-receptors, and that may limit the efficacy of mixed serotonin/noradrenaline reuptake inhibition in subacute antidepressant treatments.
Rénéric
Jean-Philippe
JP
Laboratoire de Neuropsychobiologie des Désadaptations, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5541, BP31, Université Bordeaux 2, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France. jean-philippe.reneric@labopsy.u-bordeaux2.fr
Bouvard
Manuel
M
Stinus
Luis
L
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D015259:Dopamine Agents; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000494:pharmacology; D007103:Immobilization / Q000502:physiology; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013550:Swimming / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D015259:Dopamine Agents; D005473:Fluoxetine; D008803:Mianserin; D000078785:Mirtazapine; D009638:Norepinephrine; D016627:Oxidopamine; D017367:Selective Serotonin Reuptake Inhibitors