Effects of intracerebroventricular administration of 7-nitroindazole on tolerance to ethanol.
Previous studies have shown that nitric oxide (NO) is involved in the development of rapid tolerance to the motor incoordination produced by ethanol. In order to further investigate this involvement, three experiments were undertaken using the tilt-plane and the hypothermia tests. The first demonstrated that 7-nitroindazole (7-NI), a preferential neuronal NO synthase (nNOS) inhibitor, injected by intracerebroventricular (i.c.v.) route, blocked the development of rapid tolerance to ethanol-induced motor incoordination. This effect was prevented by i.c.v. injection of L-arginine. The second experiment showed that D-arginine did not influence the blockade of tolerance produced by 7-NI. The third experiment revealed that i.c.v. injection of 7-NI also blocked the development of tolerance to the hypothermic effect of ethanol. These results support the hypothesis that nNOS-derived NO participates in the development of rapid tolerance to ethanol.
Wazlawik
Elisabeth
E
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Rua Ferreira Lima 82, 88015-420 Florianópolis, SC, Brazil.
Morato
Gina S
GS
D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D001259:Ataxia / Q000139:chemically induced / Q000517:prevention & control*; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol / Q000633:toxicity*; D007035:Hypothermia / Q000139:chemically induced / Q000517:prevention & control*; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D007191:Indazoles; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D000431:Ethanol; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C080122:7-nitroindazole