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 prefron tal cortex, the two major excitatory inputs to the striatum, modulate the n itric oxide/cyclic GMP pathway in rat striatum. Electrical stimulation (10 pulses of 0.5 ms, 10 V applied at 10 Hz, 140 mu A) 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 stimulati on to the prefrontal cortex for a total duration of 20 min did not affect s triatal cyclic GMP levels. The facilitatory effect observed after electrica l stimulation of the parafascicular thalamic nucleus was blocked by co-perf usion with tetrodotoxin, suggesting that the effect is mediated by neuronal process(es). The non-competitive N-methyl-D-aspartate receptor antagonist, dizocilpine maleate (30 mu M infused into the dorsal striatum), and the co mpetitive one, 3-[(R)-carboxypiperazin-4-yl]-propyl-phosphonic acid (50 mu M infused), but not local perfusion of the alpha-amino-3-hydroxy-5-methyl-i soxazole-4-acid antagonist, 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dio ne (15 mu M perfused locally), abolished the cyclic GMP response in the str iatum. The nitric oxide synthase inhibitor, 7-nitroindazole, applied locall y (1 mM), blocked the electrically evoked increase in striatal extracellula r cyclic GMP. This increase was also prevented by local application (100 an d 300 mu M) of 1H-(1,2,4)-oxadiazolo-(4,3a)-quinoxalin-1-one, a selective i nhibitor of soluble guanylyl cyclase. The results provide direct functional evidence of selective thalamic facili tation of the nitric oxide/cyclic GMP pathway in the dorsal striatum, throu gh activation of N-methyl-D-aspartate receptors. (C) 1999 IBRO. Published b y Elsevier Science Ltd.