Nitric Oxide‐Related Agents Alter Alcohol Withdrawal in Male Rats

Evidence has been reported supporting the hypothesis that nitric oxide (NO) partially mediates the expression of morphine dependence. To examine whether NO‐related agents also affect the expression of alcohol dependence, adult male rats were treated chronically with alcohol. Upon withdrawal of alcohol administration, abstinence signs were observed after treatment with a NO synthase (NOS) inhibitor, N^G‐nitro‐l‐arginine methyl ester (NAME), or a NO donor, isosorbide dinitrate (ISDN). Withdrawal severity was based primarily on the presence and intensity of tremors, rigidity, hyperactivity, and spontaneous and audiogenic convulsions. The NOS inhibitor, NAME (10–100 mg/kg), injected during alcohol withdrawal significantly inhibited withdrawal severity decreasing the intensity of signs of hyperactivity, tremors, and rigidity, but not affecting the occurrence of convulsions. The NO donor, ISDN (30 mg/kg), administered during alcohol withdrawal significantly increased the severity of most withdrawal signs. These results suggest that NO mediates some aspects of the expression of alcohol dependence.