Vigilance and EEG power in rats: effects of potent inhibitors of the neuronal nitric oxide synthase.
We examined the effects of potent neuronal nitric oxide synthase inhibitors, 3-bromo-7-nitro indazole (3-Br-7-NI) and S-methyl-L-thiocitrulline (S-Me-TC) on general behaviour, vigilance stages and electroencephalographic (EEG) power spectra in rats. In addition, we studied the effect of 7-nitro indazole (7-NI) on EEG power spectra in rats during dark and light periods. 3-Br-7-NI induced ptosis and decrease of slow wave sleep and rapid eye movement sleep in the rat. 7-NI and 3-Br-7-NI reduced the EEG power density in all frequency bands in the rat, suggesting a depression of central neuronal activity. This effect of 7-NI was more prominent during the day than during the night, indicating a circadian variation in the nitric oxide synthase (NOS) response to NOS inhibitor. EEG power was the most reduced in the 7-9 Hz range of the rhythmic slow activity (theta rhythm), which is in accordance with decreased locomotion observed following administration of NOS inhibitors. Although S-Me-TC is the most potent NOS inhibitor in vitro experiments, it had less effect on vigilance and EEG power in the rat than other NOS inhibitors used in this study, probably due to its short lasting and blood pressure raising effect. The present results indicate that nitric oxide exerts an excitatory and circadian dependent effect in the central neuronal structures involved in the regulation of vigilance.
Dzoljic
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Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
van Leeuwen
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de Vries
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Dzoljic
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D000818:Animals; D001143:Arousal / Q000187:drug effects*; D002648:Child; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D004576:Electromyography / Q000187:drug effects; D006801:Humans; D007191:Indazoles / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
C106731:3-bromo-7-nitroindazole; D007191:Indazoles; D002956:Citrulline; D019001:Nitric Oxide Synthase; D013890:Thiourea; C086717:S-methylthiocitrulline; C080122:7-nitroindazole; D004121:Dimethyl Sulfoxide