Effects of agmatine on ethanol withdrawal syndrome in rats

Effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, have been investigated on the ethanol withdrawal syndrome in rats. Adult male Wistar rats were used in the study. Ethanol (7.2% v/v) was given to the rats by a liquid diet for 21 days. Agmatine (20, 40, 80 and 160 mg/kg) and saline were injected to rats intraperitoneally 30 min before ethanol withdrawal testing. After 30th min, 2nd and 6th h of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, stereotyped behavior, wet dog shakes and tremor were recorded or rated. A second series of injections was given at 6 h after the first one, and subjects were then tested for audiogenic seizures. Agmatine caused dose-dependent and significant inhibitory effects on stereotyped behaviors, wet dog shakes and tremors during the observation period. It did not cause any significant change in motor coordination of naive (not ethanol-dependent) rats. Our results suggest that agmatine attenuates withdrawal syndrome in ethanol-dependent rats; thus, this drug may be beneficial in the treatment of ethanol dependence.