Effects of calcium channel blockers on impairment of brain function in senescence-accelerated mice.

Abstract

The effects of the L-type calcium channel blockers, nicardipine, nimodipine, nilvadipine and amlodipine, on brain dysfunction were examined in senescence-accelerated-prone mice. A disturbed brain function in passive avoidance response, forced swimming, rota-rod and traction tests was observed in senescence-accelerated-prone mice compared to senescence-accelerated-resistant mice. A single oral administration of the four calcium channel blockers tested had little effect on the brain dysfunction in senescence-accelerated-prone mice. In contrast, the daily oral administration of nicardipine (1 and 3 mg/kg), nimodipine (3 mg/kg) and nilvadipine (3 mg/kg), once a day for three weeks, prolonged the shortened latency of step-through in the passive avoidance response and falling time in rota-rod tests. Brain dysfunction in forced swimming and traction tests was not influenced by repeated administration of these blockers. Repeated administration of amlodipine for three weeks in senescence-accelerated-prone mice showed little pharmacological actions in all four tests. Thus, we found that repeated administration of nicardipine, nimodipine and nilvadipine ameliorated the brain dysfunction in these mice. Furthermore, the present study suggests that senescence-accelerated-prone mice can be used as an appropriate model for evaluating the pharmacological effects of calcium channel blockers on brain dysfunction.