EFFECT OF CALCIUM-CHANNEL BLOCKERS ON WITHDRAWAL SYNDROME OF LORAZEPAM IN RATS

Effects of calcium channel blockers were investigated on withdrawal si gns in lorazepam dependent rats. Physical dependence was produced by g iving lorazepam admired with the food in the following dose schedule: 10x4, 20x4, 40x4, 80x4 and 120x7 (mg/kg daily x days). Parameters such as body weight, food intake, spontaneous locomotor activity (SI,A), b ody temperature, reaction time to pain, foot shock-aggression (FSA) an d audiogenic seizures were observed during the period of administratio n of lorazepam and after its withdrawal. Calcium channel blockers viz. verapamil, nifedipine and nimodipine in different doses were administ ered orally twice daily in separate groups during the withdrawal perio d. The withdrawal signs observed in control group (without calcium cha nnel blockers) were hyperkinesia, hyperthermia, hyper-aggression and a udiogenic seizures, The administration of verapamil (5-20 mg/kg), nife dipine (1.75-7 mg/kg) and nimodipine (5-20 mg/kg) during the withdrawa l period of lorazepam showed dose dependent significant blockade of al l the withdrawal signs. Audiogenic seizures were completely blocked by 20 mg/kg dose of verapamil and nimodipine while nifedipine was partia lly effective. It may be concluded that calcium channel blockers exert protective effects on benzodiazepine withdrawal syndrome.