1. Serotonin transporter in substance P (neurokinin 1) receptor knock-out mice.
- Author
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David DJ, Froger N, Guiard B, Przybylski C, Jego G, Boni C, Hunt SP, De Felipe C, Hamon M, Jacquot C, Gardier AM, and Lanfumey L
- Subjects
- Animals, Autoradiography, Citalopram pharmacology, Extracellular Fluid metabolism, Frontal Lobe drug effects, Frontal Lobe metabolism, Hippocampus drug effects, Hippocampus metabolism, Membrane Glycoproteins genetics, Membrane Transport Proteins genetics, Mice, Mice, Knockout, Microdialysis, Nerve Tissue Proteins genetics, RNA, Messenger analysis, RNA, Messenger metabolism, Raphe Nuclei drug effects, Reverse Transcriptase Polymerase Chain Reaction, Serotonin analysis, Serotonin Plasma Membrane Transport Proteins, Selective Serotonin Reuptake Inhibitors pharmacology, Membrane Glycoproteins metabolism, Membrane Transport Proteins metabolism, Nerve Tissue Proteins metabolism, Raphe Nuclei metabolism, Receptors, Neurokinin-1 genetics, Serotonin metabolism
- Abstract
We recently demonstrated that mice lacking the gene for substance P (neurokinin 1) receptors (NK1-/-) show improved cortical dialysate serotonin (5-HT) responses to paroxetine [J. Neurosci. 21 (2001) 8188]. To test for changes that may involve the 5-HT transporter (5-HTT) in these mutant mice, in vivo/in vitro studies were performed. Autoradiographic quantification of 5-HTT was performed: [3H]citalopram binding did not reveal any modification of 5-HT binding sites in the dorsal raphe nucleus (DRN) of wild-type NK1+/+ control and mutant NK1-/- mice. These results were further confirmed by 5-HTT mRNA quantification using competitive reverse transcription and polymerase chain reaction (RT-PCR) assay, which showed similar messenger levels in the DRN of both mice genotypes. The functional status of 5-HTT in vivo was tested by using the zero net flux method of quantitative microdialysis in two serotonergic nerve terminal regions, the frontal cortex and ventral hippocampus, of wild-type NK1+/+ and NK1-/- mice. Neither basal extracellular 5-HT levels nor the 5-HT extraction fraction of the probe (Ed an index of 5-HT uptake in vivo) differed between wild-type and mutant mice in the two brain regions studied. These results suggest that no compensatory response to the constitutive deletion of the tachykinin NK1 receptor involving changes in the activity of the selective 5-HT transporter occurred in the DRN, frontal cortex and ventral hippocampus in mice.
- Published
- 2004
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