Chronic administration of the Ca(2+) channel blocker amlodipine facilitates learning and memory in mice

Acute administration of the Ca(2+) channel antagonist amlodipine has been shown to facilitate memory for several types of learning in adult animals and to improve retention in aging mice. This study reports three experiments investigating the effect of chronic amlodipine treatment on retention in mice. In the first experiment, groups of mice were treated with either amlodipine or vehicle once a day for 14 days prior to training on a spatial discrimination task. Immediately after training, animals were given a single dose of amlodipine or the vehicle and tested for retention 24 h later. Both groups showed facilitated retention, thereby demonstrating that chronic amlodipine treatment did not produce desensitization to the facilitating effects of a post training treatment. In the second experiment, chronic treatments were administered once daily for 14 days beginning 24 h after training on one-way active avoidance and retention was tested on day 15. Results showed that chronic amlodipine attenuated spontaneous forgetting, but surprisingly, a similar enhancement could be achieved by a single treatment administered 1 day after training. In the third experiment, amlodipine was given either before or immediately after 10 daily training sessions in the one-way active avoidance task. Results showed that chronic treatment accelerated rate of learning. These findings confirm the memory facilitating properties of amlodipine under conditions of chronic drug administration.