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

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.