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 rig ht or the left arm on the training session (T1) followed by a free choice t est (T2) at varying intervals after the initial trial. Untreated animals gi ven one forced trial exhibited significantly greater levels of SA than chan ce at all delay intervals out to 20 min but not at 30, 60, or 180 min. Anim als given four forced trials showed significant levels of SA 24 h after exp osure but not at 72 h. Additional groups of mice were treated with amlodipi ne, nimodipine, diltiazem, and verapamil 1 h before T1. Mice given one forc ed trial were tested 30, 60, or 180 min after T1 while mice given four forc ed trials were tested 72 h after TI. Results showed that all of the CCA's e xcept verapamil produced significant SA at the 30-min interval and nimodipi ne and diltiazem also significantly increased SA at the 60-min-delay interv al. No significant effects were observed at the 180-min test. In the four t rial groups, all of the CCA's with the exception of verapamil produced sign ificant levels of SA at the 72-h interval. These results indicate that repr esentative CCA's from both the dihydropyridine and the benzothiazapine clas ses can facilitate both short- and long-interval SA, thereby providing furt her confirmation that CCA's can enhance memory processing in young animals. (C) 2001 Academic Press.