IMPORTANCE OF FOREBRAIN CHOLINERGIC AND GABAERGIC SYSTEMS TO THE AGE-RELATED DEFICITS IN WATER MAZE PERFORMANCE OF RATS

The present study investigated the performance of rats at 3-4 months a nd 21 months of age in the Morris water maze and correlated age-relate d cognitive deficits with changes in both cholinergic and GABAergic sy stems in the frontal cortex. The older rats were divided into two grou ps, unimpaired old and impaired old according to their ability to find a hidden submerged platform in the water maze, for electrophysiologic al, neurochemical, and morphological studies. The firing rate of front al cortical neurones was recorded from the motor area of the frontal c ortex under urethane anaesthesia and was found to be significantly slo wer in the two aged groups of rats compared to the young rats, but the re were no differences between the two aged groups. The sensitivity of frontal cortex neurones of the impaired and unimpaired old age groups to ACh and to carbachol was significantly lower than that of the youn g group, but there were no differences between the two old age groups. In contrast, sensitivity of frontal cortex neurones to bicuculline wa s significantly higher in the aged rats compared with the young rats a nd was significantly greater in the impaired old rats than in the unim paired old rats. The sensitivity of cortical neurones to glutamate was unaffected by age. There were also significant correlations between t he percentages of cortical neurones responding to ACh and bicuculline and different parameters of water maze acquisition during days 7-8, bu t not during days 2-3, when spatial learning had not begun, and days 1 3-14, when spatial learning was complete. Biochemical and morphologica l analyses did not show any significant differences in ChAT activity a nd AChE-positive fibre density in the frontoparietal cortices of the t hree groups of rats. The results demonstrate that the learning deficit observed in old age rats cannot be adequately explained solely by a r eduction in cholinergic receptor sensitivity and that an age-related i ncrease in GABAergic tone may be a more important determinant of cogni tive impairment.