Effects of nitric oxide-active drugs on the discharge of subthalamic neurons: microiontophoretic evidence in the rat.

6533b823fe1ef96bd127f6e1

RESEARCH PRODUCT

Effects of nitric oxide-active drugs on the discharge of subthalamic neurons: microiontophoretic evidence in the rat.

Pierangelo Sardo Valerio Rizzo Fabio Carletti Giuseppe Ferraro Stefania D'agostino

subject

Male Time Factors Action Potentials Neurotransmission Inhibitory postsynaptic potential Nitric Oxide Settore BIO/09 - Fisiologia Nitric oxide S-Nitrosoglutathione chemistry.chemical_compound Subthalamic Nucleus Animals Nitric Oxide Donors Enzyme Inhibitors Rats Wistar Cyclic GMP Neurons Analysis of Variance Iontophoresis Dose-Response Relationship Drug Chemistry General Neuroscience 8-Br-cGMP L-NAME SIN-1 SNOG subthalamic nucleus Iontophoresis Thionucleotides Rats Enzyme Activation Subthalamic nucleus NG-Nitroarginine Methyl Ester Molsidomine S-Nitrosoglutathione Excitatory postsynaptic potential Soluble guanylyl cyclase Neuroscience

description

The presence of nitric oxide (NO) synthase and of soluble guanylyl cyclase, the main NO-activated metabolic pathway, has been demonstrated in many cells of the subthalamic nucleus. In this study, the effects induced on the firing of 96 subthalamic neurons by microiontophoretically administering drugs modifying NO neurotransmission were explored in anaesthetized rats. Recorded neurons were classified into regularly and irregularly discharging on the basis of their firing pattern. Nω-nitro-l-arginine methyl ester (L-NAME; a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1; a NO donor), S-nitroso-glutathione (SNOG; another NO donor) and 8-Br-cGMP (a cell-permeable analogue of cGMP, the main second-messenger of NO neurotransmission) were iontophoretically applied while performing single-unit extracellular recordings. The activity of most neurons was influenced in a statistically significant way: in particular, both current-related inhibitory L-NAME-induced effects (20/39 tested cells) and excitatory effects of SIN-1 (25/41 tested neurons), SNOG (19/32 tested cells) and 8-Br-cGMP (13/19 tested neurons) were demonstrated. Neither statistically significant differences between the responses of regularly and irregularly discharging cells, nor specific topographical clustering of responding neurons, were demonstrated. Neurons administered drugs oppositely modulating the NO neurotransmission often displayed responses to only one treatment. We hypothesize that NO neurotransmission could exert a modulatory influence upon subthalamic neurons, with a prevalent excitatory effect. However, in the light of the presence of some responses of opposite sign to the same drug displayed by different subthalamic neurons, more complex effects of NO neurotransmission could be suggested, probably due to interactions with other classical neurotransmitter systems. © The Authors (2006).

year	journal	country	edition	language
2006-10-17

10.1111/j.1460-9568.2006.05097.x http://hdl.handle.net/10447/20107