Intensity of GABA-evoked responses is modified by nitric oxide-active compounds in the subthalamic nucleus of the rat: A microiontophoretic study

Authors

  • Pierangelo Sardo,

    Corresponding author
    1. Dipartimento di Medicina Sperimentale—Sezione di Fisiologia umana, Università degli Studi di Palermo, Palermo, Italy
    • Dipartimento di Medicina Sperimentale—Sezione di Fisiologia umana, Università degli Studi di Palermo, Corso Tukory 129, 90134 Palermo, Italy
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  • Fabio Carletti,

    1. Dipartimento di Medicina Sperimentale—Sezione di Fisiologia umana, Università degli Studi di Palermo, Palermo, Italy
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  • Stefania D'Agostino,

    1. Dipartimento di Medicina Sperimentale—Sezione di Fisiologia umana, Università degli Studi di Palermo, Palermo, Italy
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  • Valerio Rizzo,

    1. Dipartimento di Medicina Sperimentale—Sezione di Fisiologia umana, Università degli Studi di Palermo, Palermo, Italy
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  • Vittorio La Grutta,

    1. Dipartimento di Medicina Sperimentale—Sezione di Fisiologia umana, Università degli Studi di Palermo, Palermo, Italy
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  • Giuseppe Ferraro

    1. Dipartimento di Medicina Sperimentale—Sezione di Fisiologia umana, Università degli Studi di Palermo, Palermo, Italy
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Abstract

We have previously described modulatory effects of nitric oxide (NO)–active drugs on subthalamic nucleus (STN) neurons. In this study, the effects of microiontophoretically applied NO-active compounds on GABA-evoked responses were investigated in subthalamic neurons extracellularly recorded from anesthetized rats: 45 of 62 cells were excited by S-nitroso-glutathione (SNOG), an NO donor, whereas 28 of 43 neurons were inhibited by Nω-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Nearly all neurons responding to SNOG and/or L-NAME showed significant inhibitory responses to the administration of iontophoretic GABA. In these cells, the changes induced by NO-active drugs in the magnitude of GABA-evoked responses were used as indicators of NO modulation. In fact, when an NO-active drug was co-iontophoresed with GABA, significant changes in GABA-induced responses were observed: generally, decreased magnitudes of GABA-evoked responses were observed during continuous SNOG ejection, whereas the administration of L-NAME enhanced GABA responses. In contrast, glutamate-evoked responses were enhanced by SNOG and dampened by L-NAME co-iontophoresis. Furthermore, the iontophoretic administration of bicuculline (a GABAA receptor antagonist) completely abolished the GABA-evoked inhibitory responses and reduced the magnitude of both the SNOG- and L-NAME-induced effects. The results suggest that the NO-mediated modulation of subthalamic neurons could also be a result of an interaction between NO and GABAA neurotransmission. Increased NOS activity has been shown in the hyperactive STN neurons of parkinsonian patients; on the basis of our observations about the influence of NO-active drugs on the baseline and GABA-evoked activity of subthalamic cells, such hyperactivity suggests the involvement of increased NO levels and reduced sensitivity to GABA. © 2009 Wiley-Liss, Inc.

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