The effects of calcium channel antagonists on short- and long-term retention in mice using spontaneous alternation behavior.

The effect of calcium channel antagonists (CCA's) on working and reference memory in mice was studied using spontaneous alternation (SA) behavior in a T maze. Mice were given either one or four forced trials to either the right or the left arm on the training session (T1) followed by a free choice test (T2) at varying intervals after the initial trial. Untreated animals given one forced trial exhibited significantly greater levels of SA than chance at all delay intervals out to 20 min but not at 30, 60, or 180 min. Animals given four forced trials showed significant levels of SA 24 h after exposure but not at 72 h. Additional groups of mice were treated with amlodipine, nimodipine, diltiazem, and verapamil 1 h before T1. Mice given one forced trial were tested 30, 60, or 180 min after T1 while mice given four forced trials were tested 72 h after T1. Results showed that all of the CCA's except verapamil produced significant SA at the 30-min interval and nimodipine and diltiazem also significantly increased SA at the 60-min-delay interval. No significant effects were observed at the 180-min test. In the four trial groups, all of the CCA's with the exception of verapamil produced significant levels of SA at the 72-h interval. These results indicate that representative CCA's from both the dihydropyridine and the benzothiazapine classes can facilitate both short- and long-interval SA, thereby providing further confirmation that CCA's can enhance memory processing in young animals.