title: In the rat forced swimming test, NA-system mediated interactions may prevent the 5-HT properties of some subacute antidepressant treatments being expressed.
abstract: 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.
authors.affiliation: 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
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rénéric
authors.forename: Manuel
authors.initials: M
authors.lastname: Bouvard
authors.forename: Luis
authors.initials: L
authors.lastname: Stinus
mesh_terms: 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
chemical_list: 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