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 GABAA 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 GABAA receptor binding characteristics in discrete areas of brain regions by using autoradiographic techniques. The GABAA 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.