title: Norepinephrine transporter (NET) knock-out upregulates dopamine and serotonin transporters in the mouse brain.
abstract: The noradrenaline, serotonin and dopamine transporters are three main transporters, which are the target of the antidepressant drugs. In the present study we demonstrate that the life-long deletion of the noradrenaline transporter (NET) induced up-regulation of two other monoamine transporters, dopamine and serotonin (DAT and SERT, respectively). An increase in the binding of [(3)H]paroxetine to the SERT and [(3)H]GBR12935 to the DAT was observed in various brain regions of NET-KO mice, without alterations of mRNA encoding these transporters, as measured by in situ hybridization. This important finding impacts the interpretation of previous data indicating the supersensitizity of NET-KO mice for psychostimulants or stronger effect of citalopram in behavioral tests. While using the NET-KO mice in various psychopharmacological studies is very important, one has to be aware that these mice lack NET from the earliest period of their existence, thus compensatory alterations do take place and have to be considered when it comes to interpretation of the obtained results.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Solich
authors.forename: Agata
authors.initials: A
authors.lastname: Faron-Gorecka
authors.forename: Maciej
authors.initials: M
authors.lastname: Kusmider
authors.forename: Paulina
authors.initials: P
authors.lastname: Palach
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gaska
authors.forename: Marta
authors.initials: M
authors.lastname: Dziedzicka-Wasylewska
mesh_terms: D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D017374:Paroxetine / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D017374:Paroxetine