23 Table II Age at which a cognitive
impairment can be detected in the rat according to the different behavioral tests used. With appropriate tests, a deficit can be detected early on, starting from 14 months of age. Fisher-344 rats show cognitive impairment slightly buy Ixazomib earlier than other strains, but by 16 to 18 months of age some subtle deficits can be observed in both sexes of most strains. The strain differences in water maze acquisition and recall were extensively investigated by Wyss et al24 comparing Sprague-Dawley, Wistar-Kyoto, and spontaneously hypertensive rats (SHRs) in the Morris water maze paradigm. Sprague-Dawley rats showed that spatial Inhibitors,research,lifescience,medical learning began to decline between 12 and 18 months of age and fell off precipitously between 18 and 24 months of age. Both Wistar-Kyoto Inhibitors,research,lifescience,medical and SHR strains already showed impairment at 12 months of age. In 14- to 19-month-old rats, many of the features that should characterize the MCI animal model, listed in Table
I, are present: first, by definition, old age, then the subtle memory impairment Inhibitors,research,lifescience,medical and mild neuropathological changes. Among the latter, astrogliosis has been described in aging Wistar rats,25 a loss of cholinergic neurons has already been observed in cognitively impaired rats at 14 months of age,18 and a large decrease in acetylcholine (ACh) release from the cerebral cortex, hippocampus, and striatum has been reported in 19-month-old Wistar rats.26 Inhibitors,research,lifescience,medical Moreover, in
the age range of 14 to 19 months, the motor activity and feeding behavior of the rats are still similar to those of young adult rats. It should be mentioned that Gallangher27 explicitly considers age-related cognitive decline in rats as a “naturally occurring animal model of MCI.” Aging rats have been widely used for testing drugs potentially useful for Inhibitors,research,lifescience,medical treating memory deficits and senile dementia. A few examples of drug-induced memory improvement, taken from the author’s experience, will be mentioned. A recovery of age-associated impairment in the acquisition of a passive avoidance response was observed in 18-month-old rats treated with phosphatidylserine intraperitoneally (IP) for 7 days.28 Olopatadine Nerve growth factor (NGF), administered intracerebroventricularly (ICV) for 14 days, restored age-impaired object recognition in 20-month-old rats.29 A single administration of aniracetam was able to restore object recognition in 22-month-old rats.12 Drugs aimed to facilitate learning may have no effect in young rats, but improve the performance in aging rats and the size of the improvement is, to some extent, proportional to the severity of cognitive impairment.