Uptake and Release of Norepinephrine by Serotonergic Terminals in Norepinephrine Transporter Knock-Out Mice: Implications for the Action of Selective Serotonin Reuptake Inhibitors
| Autor: | Marc G. Caron, Gabriella Zsilla, Janos P. Kiss, E. Sylvester Vizi |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
Microdialysis Berberine Serotonin reuptake inhibitor Nerve Tissue Proteins Citalopram Pharmacology Serotonergic Hippocampus Mice Norepinephrine Receptors Adrenergic alpha-2 Fluoxetine Neurobiology of Disease medicine Animals Adrenergic alpha-Antagonists Mice Knockout Serotonin Plasma Membrane Transport Proteins Membrane Glycoproteins Norepinephrine Plasma Membrane Transport Proteins Symporters biology Chemistry General Neuroscience Membrane Transport Proteins Adrenergic alpha-2 Receptor Antagonists Electric Stimulation Frontal Lobe Mice Inbred C57BL Norepinephrine transporter Organ Specificity biology.protein Antidepressant Female Serotonin medicine.drug |
| Zdroj: | The Journal of Neuroscience. 24:7888-7894 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1506-04.2004 |
| Popis: | Our aim was to investigate the functional properties of the noradrenergic system in genetically modified mice lacking the norepinephrine transporter (NET). We measured the uptake and release of [3H]norepinephrine ([3H]NE) from hippocampal and cortical slices of NET-/-knock-out (KO) and NET+/+wild-type (WT) mice and investigated the presynaptic α2-adenoceptor-mediated modulation of NE releasein vitroandin vivo. The [3H]NE uptake was reduced to 12.6% (hippocampus) and 33.5% (frontal cortex) of WT control in KO mice. The neuronal component of this residual uptake was decreased by 79.4 and 100%, respectively, when a selective serotonin reuptake inhibitor (SSRI) citalopram was present during the loading. The more preserved neuronal release of [3H]NE (hippocampus, 28.1%; frontal cortex, 74.4%; compared with WT) almost completely disappeared in both regions (94.1 and 95.3% decrease compared with KO, respectively) in the presence of citalopram, suggesting that [3H]NE was taken up and released by serotonergic varicosities. This was further supported by the finding that the release of [3H]NE from hippocampal slices of KO mice was not modulated by the α2-adrenoceptor antagonist 7,8-(methylenedioxy)-14-α-hydroxyalloberbane HCl, whereas the endogenous release of NE measured by microdialysis was even more efficiently enhanced by this drug in NET-deficient mice. These experiments indicate that serotonergic varicosities can accumulate and release NE as a result of the heterologous uptake of transmitters. Because the diffusion of NE may be spatially limited by serotonin transporters, the SSRIs, despite their selectivity, might enhance not only serotonergic but also noradrenergic neurotransmission, which might contribute to their antidepressant action. |
| Databáze: | OpenAIRE |
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