Changes of [ 3H]muscimol, [ 3H]flunitrazepam and [ 3H]MK-801 binding in rat brain by prolonged ventricular infusion of 7-nitroindazole

Eun Young Kim, Kyu Man Shin, Soyong Jang, Seikwan Oh

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4 Scopus citations


In the present study, we have investigated the effects of prolonged inhibition of nitric oxide synthase (NOS) by infusion of neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI), to examine modulation of NMDA and GABA A receptor binding in rat brain. The duration of sleeping time was significantly increased by the pre-treatment with 7-NI (100 mg/kg) 30 min before pentobarbital (40 mg/kg) treatment in rats. However, the duration of pentobarbital-induced sleep was shortened by the prolonged infusion of 7-NI into cerebroventricle for 7 days. We have investigated the effect of NOS inhibitor on NMDA and GABA A receptor binding characteristics in discrete areas of brain regions by using autoradiographic techniques. The GABA A receptors were analyzed by quantitative autoradiography using [ 3H]muscimol and [ 3H]flunitrazepam binding, and NMDA receptor binding was analyzed by using [ 3H]MK-801 binding in rat brain slices. Rats were infused with 7-NI (500 pmol/10 μl/ h, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps. The levels of [ 3H]muscimol were markedly elevated in cortex, caudate putamen, and thalamus while the levels of [ 3H]flunitrazepam binding were only elevated in cerebellum by NOS inhibitor. However, there was no change in the level of [ 3H]MK-801 binding except decreasing in the thalamus. These results show that the prolonged inhibition of NOS by 7-NI-infusion highly elevates [ 3H]muscimol binding in a region-specific manner and decreases the pentobarbital-induced sleep.

Original languageEnglish
Pages (from-to)2221-2229
Number of pages9
JournalNeurochemical Research
Issue number12
StatePublished - Dec 2004

Bibliographical note

Funding Information:
This work was supported by KISTEP Brain Neurobiology Grant (2004).


  • autoradiography
  • flunitrazepam
  • GABA receptor
  • muscimol
  • nNOS
  • osmotic pump


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