Role of nitric oxide-dependent pathways in ethanol-induced anxiolytic effects in rats.
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 acute EtOH. We tested the effects of 7-nitroindazole, a reversible competitive inhibitor of nitric oxide synthase. We also studied 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 effect. Intrahippocampal administration of the cGMP analog, 8-Bromoguanosine cyclic 3',5'-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.
Ferreira
V M
VM
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Valenzuela
C F
CF
Morato
G S
GS
D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D002492:Central Nervous System Depressants / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D000431:Ethanol / Q000627:therapeutic use*; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D007191:Indazoles / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D007191:Indazoles; D020030:Nitric Oxide Donors; D006151:Guanosine; D009569:Nitric Oxide; D000431:Ethanol; C035169:8-bromoguanosine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole