L-Type Voltage-Dependent Calcium Channel Blocker Nifedipine Enhances Memory Retention When Infused into the Hippocampus

Wistar rats with cannulae bilaterally implanted in the CA1 region of the dorsal hippocampus were trained in a step-down inhibitory avoidance task. Through these cannulae they received an infusion of 28 or 280 ng per side of the L-type voltage-dependent calcium channel antagonist nifedipine, or of its vehicle (20% dimethyl sulfoxide in saline). The two doses of the drug were studied by administration 0 or 30 min after training; in addition, the higher dose was studied by infusion 10 min before training. A retention test was carried out 24 h after the training session. The highest dose of nifedipine administered 0 min post-training enhanced test session performance of the animals compared to the control group; the effect of the lower dose was not statistically significant. There was no effect of the drug given 30 min post-training or 10 min pretraining. Despite the inability to discriminate direct neural from indirect vascular effects, these results are consistent with previous reports on nootropic actions of the dihydropyridine class of calcium channel blockers. The data are at variance with the amnestic effect of intrahippocampal nifedipine described by Lee and Lin (1991,Life Sciences,48,1333–1340), which may be attibuted to the different range of doses studied here. This might resemble the inverted U-shaped dose–response curve observed with another dihydropyridine, nimodipine, by other authors.