Age-related Changes in [3H]Nimodipine and [3H]Rolipram Binding in the Rat Brain

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Abstract
Ageing is associated with changes in neurotransmission which might be correlated with abnormal calcium metabolism. Because there is evidence that nimodipine can enhance the learning abilities of ageing animals and rolipram can enhance the excitability of neurons, providing a functional basis for cognition-enhancing activity, age-related alterations in the binding of voltage-dependent L-type calcium channels and calcium/calmodulin-independent cyclic adenosine monophosphate-selective phosphodiesterase (cyclic-AMP PDE) were studied in 3-week- and 6-, 12-, 18- and 24-month-old Fisher 344 rats by use of receptor autoradiography. [3H]Nimodipine and [3H]rolipram were used to label the voltage-dependent L-type calcium channels and calcium/calmodulin-independent cyclic-AMP PDE, respectively. [3H]Nimodipine binding showed no obvious change in all brain areas of 12- and 18-month-old rats, as compared with 6-month-old animals. In 24-month-old rats, however, [3H]nimodipine binding increased significantly in the striatum and hippocampal CA3 sector. In contrast, [3H]rolipram binding showed no significant change in most brain areas during ageing, except for a transient change only in the hippocampal CA1 sector of 12-month-old animals. [3H]Nimodipine and [3H]rolipram binding showed a significant increase in some brain areas of 3-week-old rats compared with 6-month-old animals. The results indicate that in rats voltage-dependent L-type calcium channels are more susceptible to ageing processes than calcium/calmodulin-independent cyclic-AMP PDE. Our data also demonstrate that voltage-dependent L-type calcium channels and calcium/calmodulin-independent cyclic-AMP PDE might play roles in developmental processes. These findings might help further elucidation of the relationship between age-related neurological deficits and behavioural pharmacology including cognitive function.