Chronic administration of the Ca2+ channel blocker amlodipine facilitates learning and memory in mice

Acute administration of the Ca2+ channel antagonist amlodipine has been sho wn to facilitate memory for several types of learning in adult animals and to improve retention in aging mice. This study reports three experiments in vestigating the effect of chronic amlodipine treatment on retention in mice . In the first experiment, groups of mice were treated with either amlodipi ne or vehicle once a day for 14 days prior to training on a spatial discrim ination task. Immediately after training, animals were given a single dose of amlodipine or the vehicle and tested for retention 24 h later. Both grou ps showed facilitated retention, thereby demonstrating that chronic amlodip ine treatment did not produce desensitization to the facilitating effects o f a post training treatment. In the second experiment, chronic treatments w ere administered once daily for 14 days beginning 24 h after training on on e-way active avoidance and retention was tested on day 15. Results showed t hat 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 acti ve avoidance task. Results showed that chronic treatment accelerated rate o f learning. These findings confirm the memory facilitating properties of am lodipine under conditions of chronic drug administration. (C) 2000 Elsevier Science B.V. All lights reserved.