Psychopharmacology

, Volume 214, Issue 2, pp 537–548 | Cite as

A computer-automated touchscreen paired-associates learning (PAL) task for mice: impairments following administration of scopolamine or dicyclomine and improvements following donepezil

  • Susan J. Bartko
  • Ignasi Vendrell
  • Lisa M. Saksida
  • Timothy J. Bussey
Original Investigation
First Online:
Received:
Accepted:

Abstract

Rationale

Performance on the Cambridge Neuropsychological Test Automated Battery touchscreen paired-associates learning (PAL) test is predictive of Alzheimer’s disease and impaired in schizophrenia and chronic drug users. An automated computer touchscreen PAL task for rats has been previously established. A pharmacologically validated PAL task for mice would be a highly valuable tool, which could be useful for a number of experimental aims including drug discovery.

Objectives

This study sought to investigate the effects of systemic administration of cholinergic agents on task performance in C57Bl/6 mice.

Methods

Scopolamine hydrobromide (0.02, 0.2, and 2.0 mg/kg), dicyclomine hydrochloride (M1 receptor antagonist; 2.0, 4.0, and 8.0 mg/kg), and donepezil hydrochloride (cholinesterase inhibitor; 0.03, 0.1, and 0.3 mg/kg) were administered post-acquisition in C57Bl/6 mice performing the PAL task.

Results

Scopolamine (0.2 and 2.0 mg/kg) and dicyclomine (at all administered doses) significantly impaired PAL performance. A significant facilitation in PAL was revealed in mice following donepezil administration (0.3 mg/kg).

Conclusions

The present study shows that mice can acquire the rodent PAL task and that the cholinergic system is important for PAL task performance. M1 receptors in particular are likely implicated in normal performance of PAL. The finding that mouse PAL can detect both impairments and improvements indicates that this task could prove to be a highly valuable tool for a number of experimental aims including drug discovery.

Keywords

Alzheimer’s disease Schizophrenia Muscarinic Aricept M1 receptors Place memory Object memory 
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Notes

Acknowledgments

This work was supported by a grant from the Alzheimer’s Research Trust. S.J.B. was additionally supported by a Ruth L. Kirschstein Predoctoral Fellowship from the National Institutes of Mental Health. We also thank Jamie Simon for assistance with Figure 1.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Susan J. Bartko
    • 1
    • 2
  • Ignasi Vendrell
    • 1
    • 2
  • Lisa M. Saksida
    • 1
    • 2
  • Timothy J. Bussey
    • 1
    • 2
  1. 1.Department of Experimental PsychologyUniversity of CambridgeCambridgeUK
  2. 2.MRC and Wellcome Trust Behavioural and Clinical Neuroscience InstituteUniversity of CambridgeCambridgeUK

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