Inhibition of nitric oxide synthesis attenuates alcohol consumption in two strains of alcohol-preferring rats.
The effect of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on voluntary alcohol consumption was examined in two different strains of alcohol-preferring rats, in a continuous-access, two-bottle-choice paradigm. Compared with the vehicle, intraperitoneal injections of L-NAME significantly and dose-dependently (10, 30, and 60 mg/kg) suppressed alcohol intake and preference in both alcohol-preferring (P) and Fawn-Hooded (FH) rats. The effect of the highest dose of L-NAME was nonspecific; it caused general decreases in consumption of alcohol, water, and food. Repeated injection of L-NAME (30 mg/kg) for 4 consecutive days significantly attenuated alcohol intake, but tolerance developed after 3 days of treatment. A single administration of a high dose of L-NAME (60 mg/kg) did not influence the blood alcohol concentrations, which suggests a possible central effect. Furthermore, a moderate dose of 30 mg/kg L-NAME, which selectively inhibited alcohol intake, did not exert a significant effect on telemetrically measured heart rate, core body temperature, and gross motor activity of alcohol naive Fawn-Hooded rats. These results suggest an involvement of nitric oxide in alcohol drinking behavior. Although the true mechanism(s) of action is not yet clear, it can be speculated that L-NAME may exert its action indirectly by modulating neurotransmitters proposed to be involved in alcohol drinking and/or by influencing other neuronal factors, such as neuronal Ca2+ channels, which have been shown to be involved in alcohol drinking behavior.
Rezvani
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AH
Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27599-7175, USA.
Grady
D R
DR
Peek
A E
AE
Pucilowski
O
O
D000428:Alcohol Drinking / Q000235:genetics / Q000523:psychology*; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D051381:Rats; D013045:Species Specificity
D009569:Nitric Oxide; D000431:Ethanol; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester