Effects of flumazenil on ethanol withdrawal syndrome in rats.

Effects of flumazenil (Ro 15-1788, CAS 78755-81-4) on ethanol withdrawal syndrome (EWS) has been investigated in rats. Behavioral EWS symptoms appeared during the first 6 h of ethanol withdrawal. Flumazenil (2.5 and 10 mg/kg i.p.) increased horizontal and vertical locomotor activity significantly and also precipitated abnormal gait and agitation at the beginning of EWS in a dose dependent manner. However, thereafter it reduced the severity of abnormal posture and gait, tail stiffness, agitation and stereotyped behavior in a dose dependent manner. At the 6th hour of EWS, flumazenil (10 mg/kg) reduced total EWS score significantly, but shortened the latency of audiogenic seizures and increased the severity of wet dog shakes. Flumazenil (2.5 and 10 mg/kg) did not elicit behavioral EWS symptoms and audiogenic seizures in non-dependent (control) rats. It did not cause any significant change on locomotor activities in these groups. According to those results, certain actions of flumazenil on the experimental EWS may suggest a potential beneficial effect of this drug in the treatment of EWS in alcoholics, but its enhancing effects on some behavioral EWS symptoms and a potential proconvulsant activity may be a drawback for its use in the treatment of EWS.