The parafascicular thalamic nucleus but not the prefrontal cortex facilitates the nitric oxide/cyclic GMP pathway in rat striatum.

We investigated whether the parafascicular thalamic nucleus and the prefrontal cortex, the two major excitatory inputs to the striatum, modulate the nitric oxide/cyclic GMP pathway in rat striatum. Electrical stimulation (10 pulses of 0.5 ms, 10 V applied at 10 Hz, 140 microA) delivered bilaterally to the parafascicular thalamic nucleus for a total of 4, 10 and 20 min, time-dependently facilitated cyclic GMP output in the dorsal striatum of freely moving rats, assessed by trans-striatal microdialysis. Electrical stimulation to the prefrontal cortex for a total duration of 20 min did not affect striatal cyclic GMP levels. The facilitatory effect observed after electrical stimulation of the parafascicular thalamic nucleus was blocked by co-perfusion with tetrodotoxin, suggesting that the effect is mediated by neuronal process(es). The non-competitive N-methyl-D-aspartate receptor antagonist, dizocilpine maleate (30 microM infused into the dorsal striatum), and the competitive one, 3-[(R)-carboxypiperazin-4-yl]-propyl-phosphonic acid (50 microM infused), but not local perfusion of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid antagonist, 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (15 microM perfused locally), abolished the cyclic GMP response in the striatum. The nitric oxide synthase inhibitor, 7-nitroindazole, applied locally (1 mM), blocked the electrically evoked increase in striatal extracellular cyclic GMP. This increase was also prevented by local application (100 and 300 microM) of 1H-(1,2,4)-oxadiazolo-(4,3a)-quinoxalin-1-one, a selective inhibitor of soluble guanylyl cyclase. The results provide direct functional evidence of selective thalamic facilitation of the nitric oxide/cyclic GMP pathway in the dorsal striatum, through activation of N-methyl-D-aspartate receptors.