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Journal of Neuroscience, Vol 15, 7282-7292, Copyright © 1995 by Society for Neuroscience

ARTICLE

Age-associated impairments in a test of attention: evidence for involvement of cholinergic systems

DN Jones, JC Barnes, DL Kirkby and GA Higgins
Glaxo Unit for Behavioral Psychopharmacology, Division of Biosciences, University of Hertfordshire, Hatfield, Herts, United Kingdom.

We trained three groups of rats, young (Y; 3 months at the start of study), middle aged (MA; 15 months), and aged (AG; 22 months), in the serial five-choice serial reaction time task, a test of attention. There were clear age-related differences in task acquisition: Y acquired the task quicker than MA rats, which learned faster than AG rats. A subgroup of AG rats [AG(I)] could not reach criterion (> 80% correct, < 20% omissions under standard conditions of 0.5 sec stimulus duration, 5 sec limited hold). Accordingly, they were tested under conditions of 1 sec stimulus duration. Having acquired the task, under standard conditions both MA and AG groups were slower to make a correct response but not to collect the food reward. Furthermore, parameter changes, particularly reductions in stimulus duration and intensity, revealed further age-related changes in accuracy. Following completion of these studies, animals were trained in a simpler one-choice task. Importantly, reducing stimulus duration/intensity in this task revealed no differences between Y and MA/AG groups, although AG(I) rats were impaired. This dissociation between MA/AG impairments in the one- and five-choice task suggests that these animals may show attentional deficits compared with Y rats, which are independent of changes in sensory (visual), motor function, or motivation. Finally, the MA deficit in attention was partially reversed by tacrine pretreatment (3 mg/kg). Also scopolamine (0.01-0.075 mg/kg) and mecamylamine (0.3-5 mg/kg) pretreatment impaired choice accuracy of MA but not Y rats. Taken together, the drug studies imply that the attentional deficits may at least be partially due to changes in cholinergic function.

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