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 t he dorsal hippocampus were trained in a step-down inhibitory avoidance task. Through these cannulae they received an infusion of 28 or 280 n g 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 trai ning session. The highest dose of nifedipine administered 0 min post-t raining enhanced test session performance of the animals compared to t he control group; the effect of the lower dose was not statistically s ignificant. There was no effect of the drug given 30 min post-training or 10 min pretraining. Despite the inability to discriminate direct n eural from indirect vascular effects, these results are consistent wit h previous reports on nootropic actions of the dihydropyridine class o f 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 differen t range of doses studied here. This might resemble the inverted U-shap ed dose-response curve observed with another dihydropyridine, nimodipi ne, by other authors. (C) 1998 Academic Press.