SCOPOLAMINE IMPAIRS VISUO-SPATIAL WORKING MEMORY IN AN AGE-DEPENDENT MANNER.





J.A. Araujo, A.D.F. Chan, C. Mascella, N.W. Milgram

Department of Pharmacology, University of Toronto, Toronto, ON, M5S 1A4



Aged dogs demonstrate impairments in working memory that may be linked to cholinergic dysfunction. Previously we have found that cholinergic blockade using the non-specific muscarinic antagonist scopolamine (15 mg/kg; SC) impairs visuospatial working memory in aged dogs while sparing spatial perception and reference memory. The present study investigated age-related sensitivity of canine working memory to cholinergic blockade. Initially, six young dogs were trained on a fixed-delay two-component delayed non-matching to position task with a 30 s delay. Performance on this task was examined after administration of scopolamine (15 mg/kg; SC) at a dose that significantly impairs aged dogs on the same task. Although performance accuracy was reduced to some extent, the scopolamine-induced impairment was not significant compared to control performance suggesting that young dogs are less sensitive to the impairing effects of scopolamine on visuospatial memory performance. To investigate this age difference further, seven aged dogs (11-14 years of age) and seven young dogs (2-4 years of age) were over-trained on a novel three-component delayed non-matching to position task. Subjects were tested on a variable-delay procedure using delays of 5, 55, and 105 s. Scopolamine (15 mg/kg; SC) impaired performance in aged dogs in a delay-independent manner. The performance of young dogs was not affected at any delay, although the baseline performance level did not differ between the groups. The effect of scopolamine on the performance of young dogs was investigated on a more difficult working-memory task, the delayed non-matching to sample task, using a fixed delay of 30 s. Young dogs were impaired after scopolamine (15 mg/kg; SC) compared to control conditions, extending previous findings that scopolamine specifically impairs working memory. The present results indicate that visuospatial working memory in aged dogs is more sensitive to cholinergic blockade than in young dogs. Furthermore, sensitivity to cholinergic blockade may increase with working memory demands. These findings suggest that cholinergic transmission may be diminished in an age-dependent manner in dogs and that scopolamine-induced impairments may serve as a model for age-related cholinergic dysfunction.




Key words: scopolamine, working-memory, dog, model, cholinergic







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