Attenuation of ethanol withdrawal signs by high doses of L-arginine in rats

Alcohol Alcohol. May-Jun 2003;38(3):213-8. doi: 10.1093/alcalc/agg075.


Aims: Effects of l-arginine, a nitric oxide (NO) precursor, on ethanol withdrawal syndrome were investigated in rats.

Methods: Ethanol (7.2% v/v) was given to rats by a liquid diet for 16 days. l-Arginine (250, 500 and 1000 mg/kg) or saline were injected into rats intraperitoneally 20 min before ethanol withdrawal. All injections were repeated 30 min before the 6th h of the observation period. The effects of l-arginine on ethanol withdrawal syndrome were evaluated during the first 6 h of ethanol withdrawal.

Results: l-Arginine (250 mg/kg) potentiated significantly vertical and ambulatory locomotor activities at only the 30th minute of the observation period. l-Arginine (500 and 1000 mg/kg) inhibited behavioural signs of ethanol withdrawal significantly. l-Arginine (1000 mg/kg) also prolonged the latency and attenuated the intensity of audiogenic seizures. This dose of l-arginine also reduced both vertical and ambulatory locomotor hyperactivity of the rats from the 2nd hour of ethanol withdrawal. l-Arginine (1000 mg/kg) did not produce any significant change in the locomotor activities of the naive (non-ethanol-dependent) rats.

Conclusions: Our results indicate that l-arginine at high doses alleviates the signs of ethanol withdrawal syndrome in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / physiopathology
  • Analysis of Variance
  • Animals
  • Arginine / administration & dosage
  • Arginine / pharmacology*
  • Behavior, Animal / drug effects
  • Ethanol / adverse effects*
  • Locomotion / drug effects
  • Male
  • Nitric Oxide / metabolism
  • Rats
  • Rats, Wistar
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / physiopathology


  • Nitric Oxide
  • Ethanol
  • Arginine