Celecoxib enhances the effect of reboxetine and fluoxetine on cortical noradrenaline and serotonin output in the rat
| Autor: | Aki Falk, Daniella Johansson, Torgny H. Svensson, Monica M. Marcus |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Serotonin Dopamine Microdialysis Morpholines Serotonin reuptake inhibitor Prefrontal Cortex Pharmacology Norepinephrine Reboxetine Fluoxetine Monoaminergic medicine Animals Rats Wistar Biological Psychiatry 5-HT receptor Sulfonamides Adrenergic Uptake Inhibitors Cyclooxygenase 2 Inhibitors Drug Synergism Rats Celecoxib Pyrazoles Antidepressant Psychology Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | Progress in Neuro-Psychopharmacology and Biological Psychiatry. 39:143-148 |
| ISSN: | 0278-5846 |
| DOI: | 10.1016/j.pnpbp.2012.06.003 |
| Popis: | A substantial number of patients with major depressive disorder (MDD) do not respond adequately to current antidepressant pharmacological treatments, which are all more or less based on a gradually increased enhancement of monoaminergic neurotransmission. Although a functional deficiency in monoaminergic neurotransmission may contribute to MDD, the etiology and pathophysiology are far from clarified. Recent studies suggest that inflammatory processes may contribute, since increased levels of pro-inflammatory cytokines and prostaglandin E(2) (PGE(2)) have repeatedly been observed in a subset of patients suffering from MDD. Interestingly, adjunct treatment with the anti-inflammatory drug celecoxib, a cyclo-oxygenase-2 (COX-2) inhibitor which blocks the PGE(2)-production, has shown to enhance the efficacy of both reboxetine, a selective noradrenaline reuptake inhibitor, as well as fluoxetine, a selective serotonin reuptake inhibitor, in treatment-resistant depression. To examine the neurobiological underpinnings to the clinical observations, we here studied the acute effects of a combined treatment with celecoxib and reboxetine on noradrenaline and dopamine output, as well as celecoxib and fluoxetine on 5-HT output in the medial prefrontal cortex, using in vivo microdialysis in awake freely moving rats. Celecoxib significantly potentiated the effects of reboxetine and fluoxetine on cortical noradrenaline and 5-HT output, respectively, but not the reboxetine-induced dopamine output. Moreover, celecoxib, when given alone, enhanced 5-HT output. These findings provide, in principle, novel experimental support for the clinical utility of combined treatment with antidepressant and anti-inflammatory drugs, such as COX-2 inhibitors, in MDD. |
| Databáze: | OpenAIRE |
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