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Hippocampal serotonin-1A receptor function in a mouse model of anxiety induced by long-term voluntary wheel running

Authors

  • Johannes Fuss,

    Corresponding author
    • RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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  • Miriam A. Vogt,

    1. RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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  • Klaus-Josef Weber,

    1. Department of Radiooncology, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
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  • Teresa F. Burke,

    1. Department of Pharmacology, University of Texas Health Science Center-San Antonio, San Antonio, Texas
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  • Peter Gass,

    1. RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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    • P.G. and J.G.H. contributed equally to this work.

  • Julie G. Hensler

    1. Department of Pharmacology, University of Texas Health Science Center-San Antonio, San Antonio, Texas
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    • P.G. and J.G.H. contributed equally to this work.


Correspondence to: Johannes Fuss, Central Institute of Mental Health, J 5, 68159 Mannheim, Germany. E-mail: johannes.fuss@zi-mannheim.de

ABSTRACT

We have recently demonstrated that, in C57/Bl6 mice, long-term voluntary wheel running is anxiogenic, and focal hippocampal irradiation prevents the increase in anxiety-like behaviors and neurobiological changes in the hippocampus induced by wheel running. Evidence supports a role of hippocampal 5-HT1A receptors in anxiety. Therefore, we investigated hippocampal binding and function of 5-HT1A receptors in this mouse model of anxiety. Four weeks of voluntary wheel running resulted in hippocampal subregion-specific changes in 5-HT1A receptor binding sites and function, as measured by autoradiography of [3H] 8-hydroxy-2-(di-n-propylamino)tetralin binding and agonist-stimulated binding of [35S]GTPγS to G proteins, respectively. In the dorsal CA1 region, 5-HT1A receptor binding and function were not altered by wheel running or irradiation. In the dorsal dentate gyrus and CA2/3 region, 5-HT1A receptor function was decreased by not only running but also irradiation. In the ventral pyramidal layer, wheel running resulted in a decrease of 5-HT1A receptor function, which was prevented by irradiation. Neither irradiation nor wheel running affected 5-HT1A receptors in medial prefrontal cortex or in the dorsal or median raphe nuclei. Our data indicate that downregulation of 5-HT1A receptor function in ventral pyramidal layer may play a role in anxiety-like behavior induced by wheel running. Synapse 67:648–655, 2013. © 2013 Wiley Periodicals, Inc.

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