Intensity of GABA-evoked responses is modified by nitric oxide-active compounds in the subthalamic nucleus of the rat: a microiontophoretic study.
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 Nomega-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.
Sardo
Pierangelo
P
Dipartimento di Medicina Sperimentale-Sezione di Fisiologia umana, Università degli Studi di Palermo, Palermo, Italy. pierangelo.sardo@unipa.it
Carletti
Fabio
F
D'Agostino
Stefania
S
Rizzo
Valerio
V
La Grutta
Vittorio
V
Ferraro
Giuseppe
G
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007478:Iontophoresis / Q000379:methods; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D020531:Subthalamic Nucleus / Q000166:cytology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D026422:S-Nitrosoglutathione; D019331:NG-Nitroarginine Methyl Ester; D001640:Bicuculline