Repeated treatment with cholecystokinin octapeptide improves maze performance in aged Fischer 344 rats

Previous studies have shown that sulfated cholecystokinin octapeptide (CCK-8S) can improve learning in adult rodents when administered systemically or into the central nucleus of amygdala. Here we analyzed the effect of repeated intraperitoneal (i.p.) injection of CCK-8S on the performance of 26-month-old Fischer 344 rats in different versions of the Morris water maze and in a rota-rod test of motor coordination. Old rats were injected daily with different doses of CCK-8S (0.32 to 8.0 μg/kg; IP) 10 min before the behavioral tests. Control groups included vehicle-injected old and adult (3-month-old) F 344 rats. To control for a possible development of tolerance to the behavioral effects of repeated CCK-8S administration, groups of aged rats were included which were subjected to an acute rather than a repeated CCK injection schedule. The repeated administration of CCK-8S did not influence the performance of the old rats in the hidden-platform version of the maze. In addition, the acute treatment with CCK-8S failed to modify navigation performance in this task, suggesting that drug-tolerance may not account for the lack of behavioral effects seen after repeated CCK-8S injection. During the ‘probe trial’, the percentage of animals per group, which swam exactly across the former platform site, was markedly increased in aged rats treated repeatedly with 1.6 μg/kg CCK-8S. This might be indicative of improved retention of the prior platform location and/or a higher resistance of the learned escape response to extinction. The specificity of the effect of CCK-8S on processes related to spatial learning and memory is supported by the lack of effect on motor performance.