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.
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Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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Uboldi
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D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013779:Tetrodotoxin / Q000494:pharmacology; D013787:Thalamic Nuclei / Q000502:physiology*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007191:Indazoles; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006162:Guanylate Cyclase; D006152:Cyclic GMP; C080122:7-nitroindazole