Calcium channel antagonists enhance retention of passive avoidance and maze learning in mice

Although a number of studies have shown that treatment with calcium channel antagonists (CCAs) can ameliorate impairments in learning and memory in ag ed animals, evidence for a general nootropic effect of CCAs in neurological ly normal young adult animals is ambiguous. This study attempts to resolve some of this ambiguity by comparing the effects of several CCAs on retentio n of passive avoidance learning and acquisition and retention of appetitive ly motivated spatial discrimination learning in young adult mice. Animals w ere trained in a step through passive avoidance apparatus and, immediately after training, injected subcutaneously with different doses of nimodipine, nifedipine, amlodipine, flunarazine, diltiazem, or verapamil. Retention wa s tested 24 h after training. In the maze-learning task mice were treated w ith the same doses of the aforementioned CCAs immediately after a brief tra ining session in a linear maze and retention was tested 24 h after training . The most effective dose of each agent in the maze-retention experiment wa s administered to additional groups of animals 1 h prior to training to det ermine the effects of CCAs on acquisition processes. The effects of central administration of CCAs were examined by intracerebroventricular injection of different doses of amlodipine immediately after passive avoidance traini ng. Results showed (1) all peripherally administered drugs except verapamil facilitated retention of passive avoidance training in a dose-dependent ma nner, (2) all drugs dose dependently facilitated retention of linear maze l earning, (3) all doses of the drugs (except verapamil) which facilitated ma ze retention also facilitated maze learning, and (4) central administration of the dihydropyridine amlodipine produced a dose-dependent facilitation o f the retention of passive avoidance learning. These data indicate that dru gs which block calcium channels can enhance retention of two different type s of learning in mice. (C) 2001 Academic Press.