Scopolamine induced deficits in a battery of cognitive tests: Comparisons of sensitivity and specificity

Date of Completion

January 2006

Keywords

Biology, Neuroscience

Degree

Ph.D.

Abstract

Scopolamine hydrobromide (HBr), a cholinergic antagonist, has been used to model dementia in a number of preclinical cognitive tests, in order to assess the potential efficacy of novel compounds. However, differences between these behavioral tests in terms of their sensitivity and specificity to scopolamine-induced cognitive deficits have not been systematically determined. Objective. Using a single group of rats, the present experiments compared the effects of scopolamine on a behavioral battery of tasks: Morris water maze (MWM), radial arm maze (RAM), delayed non-matching to position (DNMTP) tasks, and fixed-ratio 5 bar pressing (FR5). The behavioral battery ranged from tasks thought to have little cognitive demand to those thought to be based on more attention and spatial working memory. Control studies in other animals assessing peripheral versus central effects were conducted using both liquid and dry reinforcement and utilizing methyl scopolamine. Further, 5-choice serial reaction time test (5-CSRT T) assessed scopolamine effects on attention. Results. In the MWM, scopolamine produced small, specific cognitive deficits. In the RAM and DNMTP, scopolamine produced small deficits in spatial working memory but robust deficits in psychomotor processes or attention (e.g. rate of arm entries and response latencies). Further other results indicated a wide spectrum of central and peripheral cholinergic involvement. The central effects include attention and motor initiation both of which impact and interact with the mnemonic function of acetylcholine. Conclusions. Taken together the results indicate that these cognitive tasks are good at determining the effect of hippocampal lesions or drugs on abilities such as attention, working and reference memory. However this determination is more valid on a group level than when examining individual animals. To reliably establish the abilities of individuals, animals theymust be well trained in the task and tested repeatedly. Further the results indicate a wide spectrum of both central and peripheral cholinergic involvement in behavior. The central effects include attention and motor initiation both of which impact and interact with the mnemonic function of acetylcholine. These results demonstrate a limited disruption of the central cholinergic system can have profound effects on attention and/or psychomotor control before any measurable mnemonic disruption. ^

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