A. Batuecas et al., EFFECTS OF CHRONIC NIMODIPINE ON WORKING-MEMORY OF OLD RATS IN RELATION TO DEFECTS IN SYNAPTOSOMAL CALCIUM HOMEOSTASIS, European journal of pharmacology, 350(2-3), 1998, pp. 141-150
The present study was designed to investigate whether chronic (from 12
to 23 months of age) dietary treatment with the L-type Ca2+ channel b
locker nimodipine (30 mg/kg body weight) enhances the cognitive behavi
or of aged animals and whether such a treatment would have long-term e
ffects on the mechanisms of Ca2+ regulation in synaptic terminals from
the aged rat brain. Cognitive behavior was evaluated in an 8-arm radi
al maze in 6 test series comprising a total of 105 test sessions, with
intervals of no training between series. Nimodipine-treated rats perf
ormed better than vehicle-treated, aged matched controls in all the te
st series, making more correct choices every time a new series was ini
tiated. However, differences between nimodipine- and vehicle-treated r
ats 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 ra
ts 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+ r
egulation in synaptosomes derived from cerebral cortex and hippocampus
, we analyzed Ca-45(2+) 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 b
ut increased the levels of calbindin-D28K and calreticulin in cerebral
cortex preparations. These results indicate that chronic nimodipine t
reatment from 12 to 23 months of age prevents age-induced learning def
icits without showing any signs of toxicity, and that these effects ar
e associated with a small increase in the levels of synaptosomal Ca2+-
binding proteins from cerebral cortex. The up-regulation of these prot
eins might provide a Link between the long-term effects of nimodipine
on gene expression and learning ability in old rats. (C) 1998 Elsevier
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