Serotonin transporter in substance P (neurokinin 1) receptor knock-out mice.
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.
David
Denis J
DJ
Laboratoire de Neuropharmacologie Tour D1, 2ème étage, EA 3544 MJENR, Faculté de Pharmacie IFR75-ISIT Institut de Signalisation et d'Innovation Thérapeutique, Université Paris-Sud, 5 rue J-B. Clément, F92296 Châtenay-Malabry, France.
Froger
Nicolas
N
Guiard
Bruno
B
Przybylski
Cédric
C
Jego
Gaelle
G
Boni
Claudette
C
Hunt
Stephen P
SP
De Felipe
Carmen
C
Hamon
Michel
M
Jacquot
Christian
C
Gardier
Alain M
AM
Lanfumey
Laurence
L
D000818:Animals; D001345:Autoradiography; D015283:Citalopram / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D015283:Citalopram; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493231:Slc6a4 protein, mouse