ABSTRACT: The present study was designed to investigate whether chronic (from 12 to 23 months of age) dietary treatment with the L-type Ca2+ channel blocker nimodipine (30 mg/kg body weight) enhances the cognitive behavior of aged animals and whether such a treatment would have long-term effects on the mechanisms of Ca2+ regulation in synaptic terminals from the aged rat brain. Cognitive behavior was evaluated in an 8-arm radial maze in 6 test series comprising a total of 105 test sessions, with intervals of no training between series. Nimodipine-treated rats performed better than vehicle-treated, aged-matched controls in all the test series, making more correct choices every time a new series was initiated. However, differences between nimodipine- and vehicle-treated rats were most remarkable in the last three test series, when the rats were 19 to 22 months. In these series 74% of the nimodipine-treated rats were able to perform the task in 4 to 9 test sessions whereas only 12%, 14% or none of the control rats learned the task. To study Ca2+ regulation in synaptosomes derived from cerebral cortex and hippocampus, we analyzed 45Ca2+ accumulation as well as the levels of the Ca2+-binding proteins calbindin-D28K and calreticulin by Western blotting. Nimodipine administration had no effect on hippocampal synaptosomes but increased the levels of calbindin-D28K and calreticulin in cerebral cortex preparations. These results indicate that chronic nimodipine treatment from 12 to 23 months of age prevents age-induced learning deficits without showing any signs of toxicity, and that these effects are associated with a small increase in the levels of synaptosomal Ca2+-binding proteins from cerebral cortex. The up-regulation of these proteins might provide a link between the long-term effects of nimodipine on gene expression and learning ability in old rats.
European Journal of Pharmacology 07/1998; 350(2-3):141-50. · 2.52 Impact Factor