Aim: 

In this study we evaluated the NO neuromodulatory effects on the bioelectric activity of neurons belonging to the rat substantia nigra pars reticulata (SNr), an output structure of basal ganglia (BG) system.

Methods: 

Urethane-anesthetized male Wistar rats were used. In a group of rats a single dose of the preferential neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitro-indazole (7-NI), was administered (50 mg/kg, intraperitoneally). In another group, seven-barrel glass microelectrodes filled with NO-active drugs were directed stereotaxically to the SNr to perform a microiontophoretic administration. In particular, we used L-arginine methyl ester (L-NAME), a non-specific nNOS inhibitor, and 3-morpholino-sydnonimin-hydrocloride (SIN-1), a NO donor; furthermore, we administered the 8-bromo-cyclic guanosine 3',5'-monophosphate (8Br-cGMP), an analogue of cGMP, the main second messenger of NO neurotransmission, to explore the possible involvement of the soluble form of guanylyl cyclase (sGC) in the evidenced effects.

Results: 

The results show a direct influence exerted by NO-active drugs on the discharge of SNr neurons. In particular, 7-NI caused a decrease in the firing rate of the responsive cells, while microiontophoretic application of SIN-1 showed an excitatory effect; the administration of L-NAME did not produce univocal effects. Also, we observed that the iontophoretic administration of 8-Br-cGMP mimicked the NO donor-induced excitatory effect.

Conclusion: 

We hypothesize that NO neurotransmission could exert a modulatory influence upon SNr neurons (a clear excitatory effect on most of the recorded neurons). Moreover, the 8-Br-cGMP tests suggest that the NO effects could be mediated through cGMP pathway.