Intensity of GABA-evoked responses is modified by nitric oxide-active compounds in the subthalamic nucleus of the rat: A microiontophoretic study
✍ Scribed by Pierangelo Sardo; Fabio Carletti; Stefania D'Agostino; Valerio Rizzo; Vittorio La Grutta; Giuseppe Ferraro
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 317 KB
- Volume
- 87
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
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 __N__ω‐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 GABA~A~ 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 GABA~A~ 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.