Aberrant Accumulation of Serotonin in Dopaminergic Neurons.
From: Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany. rainald.moessner@mail.uni-wuerzburg.de
Neuroscience letters
- Publish Date: Jun 2006
- ISSN: 0304-3940
- Volume: 401
- Issue: 1-2
- Pages: 49-54
- Medium: Print
- Language: English
- Citation (JAMA): Mössner Rainald, Simantov Rabi, Marx Alexander, et al. Aberrant Accumulation of Serotonin in Dopaminergic Neurons.. Neurosci. Lett. Jun 2006;401:49-54
Abstract
Gene targeting approaches greatly facilitate insight into the functioning of monoamine transporters, the targets of potent antidepressants. The serotonin transporter (5-HTT) is the molecular target of a large number of antidepressants. To assess the clearance of serotonin (5-HT) in the absence of the 5-HTT, we have generated double knockout mice lacking both the 5-HTT and the catabolizing enzyme monoamine oxidase A (MAOA). We found aberrant 5-HT accumulation in the striatum of these MAOA/5-HTT double knockout mice. By additional ablation of the dopamine transporter (DAT), this aberrant 5-HT accumulation was abolished in MAOA/5-HTT/DAT triple knockout mice. Thus, aberrant uptake of 5-HT occurs in dopaminergic terminals under conditions of elevated 5-HT levels, and this aberrant uptake is mediated by the DAT. These findings have important consequences for antidepressant therapy, since during treatment of depression with selective serotonin reuptake inhibitors, clearance of 5-HT by dopaminergic neurons may reduce the desired therapeutic elevation of extracellular 5-HT levels. This provides a molecular rationale for improving antidepressant efficacy by additional pharmacological inhibition of the DAT.
Mesh Headings (Keywords): Animals, Brain, Brain Chemistry, Depressive Disorder, Dopamine, Dopamine Plasma Membrane Transport Proteins, Female, Male, Mice, Mice, Knockout, Monoamine Oxidase, Neurons, Presynaptic Terminals, Serotonin, Serotonin Plasma Membrane Transport Proteins, Serotonin Uptake Inhibitors, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 16638624
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