title: Decreased anxiety in mice lacking the organic cation transporter 3.
abstract: The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. OCTs are a family of high-capacity, bidirectional, multispecific transporters of organic cations. These also include serotonin, dopamine and norepinephrine making OCTs attractive candidates for a variety of neuropsychiatric disorders including anxiety disorders. OCT3 has been implicated in termination of monoaminergic signalling in the central nervous system. Interestingly, OCT3 mRNA is however also significantly up-regulated in the hippocampus of serotonin transporter knockout mice where it might serve as an alternative reuptake mechanism for serotonin. The examination of the behavioural phenotype of OCT3 knockout mice thus is paramount to assess the role of OCT3. We have therefore subjected mice lacking the OCT3 gene to a comprehensive behavioural test battery. While cognitive functioning in the Morris water maze test and aggression levels measured with the resident-intruder paradigm were in the same range as the respective control animals, OCT3 knockout animals showed a tendency of increased activity and were significantly less anxious in the elevated plus-maze test and the open field test as compared to their respective wild-type controls arguing for a role of OCT3 in the regulation of fear and anxiety, probably by modulating the serotonergic tone in limbic circuitries.
authors.affiliation: Section of Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany. wultsch_t@klinik.uni-wuerzburg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Wultsch
authors.forename: Gundula
authors.initials: G
authors.lastname: Grimberg
authors.forename: Angelika
authors.initials: A
authors.lastname: Schmitt
authors.forename: Evelin
authors.initials: E
authors.lastname: Painsipp
authors.forename: Heike
authors.initials: H
authors.lastname: Wetzstein
authors.forename: Alexandra Frauke Stephanie
authors.initials: AF
authors.lastname: Breitenkamp
authors.forename: Dirk
authors.initials: D
authors.lastname: Gründemann
authors.forename: Edgar
authors.initials: E
authors.lastname: Schömig
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Manfred
authors.initials: M
authors.lastname: Gerlach
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology*; D005239:Fear / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D027701:Organic Cation Transport Proteins / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099254:Organic Cation Transporter 3
chemical_list: D027701:Organic Cation Transport Proteins; D000099254:Organic Cation Transporter 3