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Updated: Aug 24, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
Published on: February 11, 2019
Effects of acute and repeated administration of a cholinesterase inhibitor on timing behaviour
Pascale C Bouger1, Laura Spowart-Manning, Andre Ferrara
1CNS Research, Bayer AG, Aprather Weg 18a, D-42096 Wuppertal, Germany.
Abstract:
It has been hypothesised that a leftward shift in the response distribution obtained in the peak interval (PI) procedure is a characteristic of cognitive enhancement in which mental processes are speeded. Metrifonate, a cholinesterase inhibitor with reported cognitive enhancing properties in many animal models of learning and memory, was tested in the PI procedure. Acute administration of 3 and 60 mg/kg but not 1 and 30 mg/kg in fully trained rats shifted the response distribution to the right, whereas subchronic administration of 10, 30 or 50 mg/kg during task acquisition had no effect on timing behaviour. On the basis of the present data, it can be concluded that the effects of a cognition enhancer in the PI procedure cannot be predicted from the scalar expectancy theory (SET). Furthermore, SET does not appear to be an appropriate tool for analysing the acquisition of timing behaviour.
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