Bidirectional effects of the neuroactive steroid tetrahydrodeoxycorticosterone on GABA-activated Cl currents in cultured rat hypothalamic neurons

Authors

  • C H R Wetzel,

    1. Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 2, 80804 Munich, Germany
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    • 2

      Current address: Lehrstuhl für Zellphysiologie, Ruhr-Universität Bochum, D-44801 Bochum, Germany

  • H Vedder,

    1. Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 2, 80804 Munich, Germany
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    • 3

      Current address: Philipps-Universität Marburg, Klinik für Psychiatrie und Psychotherapie, D-35033 Marburg, Germany

  • F Holsboer,

    1. Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 2, 80804 Munich, Germany
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  • W Zieglgänsberger,

    1. Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 2, 80804 Munich, Germany
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  • R A Deisz

    Corresponding author
    1. Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 2, 80804 Munich, Germany
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    • 4

      Current address: Humboldt-Universität Berlin, Anatomisches Institut Charité, D-10098 Berlin, Germany


Humboldt-Universität Berlin, Anatomisches Institut Charité, D-1098 Berlin, Germany

Abstract

  • The nongenomic effects of tetrahydrodeoxycorticosterone (THDOC; 5-alpha-pregnane-3-alpha, 21-diol-20-one) were studied in cultured hypothalamic neurons of the rat.

  • The effects of THDOC (10 nM–1 μM) on responses to different concentrations of exogenously applied GABA and on spontaneous inhibitory postsynaptic currents (IPSCs) were measured with whole-cell voltage clamp recordings.

  • Application of GABA induced inward currents with dose-dependently increasing amplitudes (up to 3.9 nA at a holding potential of −20 mV). High doses of THDOC (100 nM–1 μM) induced small inward currents on its own (14±3 and 24±3 pA, respectively).

  • Simultaneous application of 10 μM GABA with 100 nM or 1 μM THDOC increased current amplitudes by 125 and 128%, respectively. At 10 nM THDOC exerted no consistent effects on GABA currents.

  • Responses to 1 μM of GABA were modulated in a bidirectional manner by different doses of THDOC: 10 nM THDOC reduced the amplitude of GABA responses to 80% (P=0.018, n=15), whereas 100 nM and 1 μM THDOC enhanced the GABA response to 115 and 180% (P=0.0007, n=15), respectively.

  • The time constant of decay of spontaneous inhibitory postsynaptic currents (IPSCs) was reversibly increased from 91±10 to 314±34 ms (n=3) by the application of THDOC (1 μM). The amplitudes of the IPSCs were not affected by THDOC.

  • These data indicate that THDOC modulates GABA responses of hypothalamic neurons in a bidirectional manner, resulting in a complex tuning of neuronal excitability in the hypothalamus.

British Journal of Pharmacology (1999) 127, 863–868; doi:10.1038/sj.bjp.0702597

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