Effect of the calcium channel blocker amlodipine on memory in mice

Five experiments were performed to investigate the effects of amlodipine, a calcium channel antagonist of the 1,4-dihydropyridine class, on consolidation and retrieval of memory in mice. In a single-trial passive avoidance task, amlodipine was administered pretraining, posttraining, or pretesting. Results of temporal and dose-response studies showed that memory enhancement (significant increase in step-through latency) occurred when amlodipine (5, 7, 9, 15, and 30 mg/kg) was given either immediately post-training or (15 mg/kg) 15 min pretesting. Using a conditioned emotional response task, tone was paired with shock using Pavlovian conditioning procedures. Strength of conditioning was assessed by measuring suppression of drinking in the presence of a tone. Amlodipine (7 mg/kg) given immediately following both high- and low-intensity shock significantly enhanced conditioned suppression. In the third experiment thirsty mice were trained on a spatial discrimination task in a linear maze. Correct choices were reinforced with liquid reinforcement. Amlodipine (10 mg/kg) injected immediately after the training session produced a significant enhancement of discrimination performance on a 24-h retention test. In the fourth experiment mice were given 25 training trials in a two-way active avoidance task and were treated with either amlodipine (10 mg/kg) or saline after training. Amlodipine-treated mice made significantly more avoidances on the test session than control animals. The final experiment demonstrated that the deficit in approach-avoidance behavior seen in 18-month-old mice could be reversed by amlodipine treatment after the training session. These studies suggest that amlodipine can facilitate memory consolidation and retrieval.