α2-Adrenergic Receptor Blockade Markedly Potentiates Duloxetine- and Fluoxetine-Induced Increases in Noradrenaline, Dopamine, and Serotonin Levels in the Frontal Cortex of Freely Moving Rats
| Autor: | Jean-Michel Rivet, Millan Mark, Laetitia Cistarelli, Alain P. Gobert, C. Melon |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Agonist Serotonin medicine.medical_specialty medicine.drug_class Dopamine Thiophenes Pharmacology Duloxetine Hydrochloride Biochemistry Reuptake Norepinephrine Cellular and Molecular Neuroscience chemistry.chemical_compound Fluoxetine Internal medicine medicine Animals Biogenic Monoamines Rats Wistar Neurotransmitter Adrenergic alpha-Antagonists Adrenergic Uptake Inhibitors Frontal Lobe Rats Monoamine neurotransmitter Endocrinology chemistry Antidepressant Reuptake inhibitor Selective Serotonin Reuptake Inhibitors |
| Zdroj: | Journal of Neurochemistry. 69:2616-2619 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1046/j.1471-4159.1997.69062616.x |
| Popis: | Evidence exists that a reinforcement in monoaminergic transmission in the frontal cortex (FCX) is associated with antidepressant (AD) properties. Herein, we examined whether blockade of alpha2-adrenergic receptors modified the influence of monoamine reuptake inhibitors on FCX levels of serotonin (5-HT), noradrenaline (NAD), and dopamine (DA). The selective alpha2-adrenergic receptor agonist S 18616 (0.16 mg/kg, s.c.) suppressed extracellular levels of NAD, DA, and 5-HT (by 100, 51, and 63%, respectively) in single dialysates of FCX of freely moving rats. In contrast, the selective alpha2-adrenergic receptor antagonists atipamezole (0.16 mg/kg, s.c.) and 1-(2-pyrimidinyl)piperazine (1-PP; 2.5 mg/kg, s.c.) increased levels of NAD (by 180 and 185%, respectively) and DA (by 130 and 90%, respectively), without affecting 5-HT levels. Duloxetine (5.0 mg/kg, s.c.), a mixed inhibitor of 5-HT and NAD reuptake, and fluoxetine (10.0 mg/kg, s.c.), a selective 5-HT reuptake inhibitor, both increased levels of 5-HT (by 150 and 120%, respectively), NAD (by 400 and 100%, respectively), and DA (by 115 and 55%, respectively). Atipamezole (0.16 mg/kg, s.c.) markedly potentiated the influence of duloxetine and fluoxetine on levels of 5-HT (by 250 and 330%, respectively), NAD (by 1,030 and 215%, respectively), and DA (by 370 and 170%, respectively). 1-PP similarly potentiated the influence of duloxetine on 5-HT, NAD, and DA levels (by 290, 1,320, and 600%, respectively). These data demonstrate that alpha2-adrenergic receptors tonically inhibit NAD and DA and phasically inhibit 5-HT release in the FCX and that blockade of alpha2-adrenergic receptors strikingly potentiates the increase in FCX levels of 5-HT, NAD, and DA elicited by reuptake inhibitors. Concomitant alpha2-adrenergic receptor antagonism and inhibition of monoamine uptake may thus provide a mechanism allowing for a marked increase in the efficacy of AD agents. |
| Databáze: | OpenAIRE |
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