Nitric oxide-active compounds modulate glutamatergic and GABAergic transmission in globus pallidus of rat

The globus pallidus (GP) of rodents, homologous to the external globus pallidus of primates, plays a critical role in the expression of basal ganglia (BG) function. Glutamatergic and GABAergic inputs have been demonstrated to greatly modulate the spontaneous GP activity. In this study the effects of local applied NO-active compounds on glutamate (GLU)- and GABA-evoked responses were investigated in rat GP neurons. Extracellularly recorded single units from anesthetized rats were treated with GLU or GABA before and during the microiontophoretic application of S-nitrosoglutathione (SNOG), a NO donor, and Nω-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Most GP cells were excited by SNOG whereas administration of L-NAME induced decrease of GP neurons activity. Nearly all neurons responding to SNOG and/or L-NAME showed significant modulation of their responses to the administration of iontophoretic GLU or GABA. Generally, increased magnitudes of excitatory GLU-evoked responses were observed during SNOG ejection, whereas the administration of L-NAME decreased responses to GLU; conversely, decreased magnitudes of inhibitory GABA-evoked responses were observed during SNOG ejection, while the GABA effect was reinforced by L-NAME administration. In these cells, the changes induced by NO-active drugs in the magnitude of GLU- or GABA-evoked responses were used as indicators of NO modulation. The results suggest that the NO-active drugs modulate the response of GP neurons to glutamatergic and GABAergic transmission. Nitrergic modulation could play an important role in the control of GP bioelectric activity, not only in normal conditions but also in pathophysiological states.