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Decreased anxiety in mice lacking the organic cation transporter 3

  • Basic Neurosciences, Genetics and Immunology - Original Article
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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.

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Authors and Affiliations

  1. Section of Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080, Würzburg, Germany

    Thomas Wultsch, Angelika Schmitt, Heike Wetzstein, Klaus-Peter Lesch, Manfred Gerlach & Andreas Reif

  2. Department of Pharmacology, University of Cologne, Cologne, Germany

    Gundula Grimberg, Alexandra Frauke Stephanie Breitenkamp, Dirk Gründemann & Edgar Schömig

  3. Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria

    Evelin Painsipp

  4. Department of Child and Adolescent Psychiatry, University of Würzburg, Würzburg, Germany

    Manfred Gerlach

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  1. Thomas Wultsch
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  2. Gundula Grimberg
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  3. Angelika Schmitt
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Correspondence to Thomas Wultsch.

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Wultsch, T., Grimberg, G., Schmitt, A. et al. Decreased anxiety in mice lacking the organic cation transporter 3. J Neural Transm 116, 689–697 (2009). https://doi.org/10.1007/s00702-009-0205-1

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