Role of Nitric Oxide-Dependent Pathways in Ethanol-Induced Anxiolytic Effects in Rats

• Published in: Alcoholism, clinical and experimental research Vol. 23; no. 12; pp. 1898 - 1904
• Main Authors: Ferreira, Vania M.M., Valenzuela, C. Fernando, Morato, Gina S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.1999; Lippincott Williams & Wilkins
• Subjects: Alcoholism and acute alcohol poisoning; Animals; Anxiety; Anxiety - drug therapy; Biological and medical sciences; Central Nervous System Depressants - therapeutic use; Drug Therapy, Combination; Elevated Plus-Maze; Enzyme Inhibitors - therapeutic use; Ethanol; Ethanol - therapeutic use; Guanosine - analogs & derivatives; Guanosine - pharmacology; Hippocampus; Hippocampus - drug effects; Indazoles - therapeutic use; Male; Medical sciences; Nitric Oxide; Nitric Oxide - physiology; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Rats; Rats, Wistar; Toxicology; Intraperitoneal administration; Ethanol; Rat; Enzyme; Psychotropic; Acute; Alcoholism; Rodentia; Central nervous system; Enzyme inhibitor; 3',5'-GMP; Nitric-oxide synthase; Vertebrata; Mammalia; Tranquillizer; Animal; Nitric oxide; Intracerebral administration; Anxiety; Oxidoreductases; Mechanism of action; Hippocampus; Brain (vertebrata)
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.1999.tb04089.x

Background: Nitric oxide (NO) is a neuromodulator and an intercellular and retrograde messenger that mediates several functions in the central nervous system. The effects of ethanol (EtOH) on neuronal NO‐dependent pathways have been the focus of recent research. Most studies have concentrated on the actions of chronic EtOH exposure. In this study, we examined the role of NO‐dependent pathways in the acute actions of EtOH. Methods: We used the elevated plus‐maze test to study the role of NO‐dependent pathways in the behavior of rats treated with acutc EtOH. We tested the effects of 7‐nitroindazole, a reversible competitive inhibitor of nitric oxide synthasc. We also studicd the effects of the cyclic guanylate monophosphate (cGMP) analog, 8‐Bromoguanosine cyclic 3′, 5′‐monophosphate sodium salt, and the NO donors S‐nitroso‐N‐acetylpenicillamine or sodium nitroprusside. Results: When injected by either intraperitoneal (6 mg/kg) or intrahippocampal (20 nmol) routes, 7‐nitroindazole increased the percentage of open arm entries and time spent in open arms for rats injected with EtOH (1.0 g/kg, ip). This dose of EtOH did not produce an anxiolytic effect when administered alone. Additional experiments were performed with a dose of 1.2 g/kg of EtOH (ip), which produced an anxiolytic effcct. Intrahippocampal administration of the cGMP analog, 8‐Bromoguanosine cyclic 3′3′‐monophosphate sodium salt (40 nmol), or the NO donors S‐nitroso‐N‐acetylpenicillamine (20 or 40 nmol) or sodium nitroprusside (20 or 40 nmol) blocked the anxiolytic effect of this dose of EtOH. Conclusions: These results indicate that inhibition of NO‐dependent pathways enhances, whereas stimulation of these pathways decreases, the efficacy of EtOH to produce anxiolytic effects in rats. We postulate that NO‐dependent increases in guanylate cyclase activity and cGMP levels oppose the anxiolytic effects produced by acute EtOH administration.