Evaluation of inhibitory effect of diphenhydramine on benzodiazepine dependence in rats

Effect of diphenhydramine was investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg, daily x days). The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock aggression (FSA) and audiogenic seizures. Diphenhydramine was administered orally in the dose schedules of once daily (10, 20 and 40 mg/kg) and twice daily (5, 10 and 20 mg/kg) in separate groups during the withdrawal period. The withdrawal signs observed in control group (without diphenhydramine) were hyperkinesia, hyperthermia, hyperaggression and audiogenic seizures. Hyperkinesia and hyperthermia were blocked in all the groups of diphenhydramine-treated rats. FSA was inhibited only by diphenhydramine (10 and 20 mg/kg) given twice daily. Audiogenic seizures were completely blocked by once daily (20 and 40 mg/kg) as well as twice daily (20 mg/kg) doses of diphenhydramine. It may be concluded that diphenhydramine exerts a protective effects on benzodiazepine withdrawal syndrome.