title: A computer-automated touchscreen paired-associates learning (PAL) task for mice: impairments following administration of scopolamine or dicyclomine and improvements following donepezil.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 (M(1) 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. M(1) 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.
authors.affiliation: Department of Experimental Psychology, University of Cambridge, Downing St., Cambridge, CB2 3EB, UK. susan.bartko.winters@gmail.com
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Bartko
authors.forename: Ignasi
authors.initials: I
authors.lastname: Vendrell
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Saksida
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bussey
mesh_terms: D000818:Animals; D001331:Automation; D001522:Behavior, Animal / Q000187:drug effects*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003463:Cues; D004025:Dicyclomine / Q000494:pharmacology*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D007189:Indans / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000494:pharmacology*; D010153:Paired-Associate Learning / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012201:Reward; D012601:Scopolamine / Q000494:pharmacology*; D013997:Time Factors; D014110:Touch; D014584:User-Computer Interface
chemical_list: D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D004025:Dicyclomine; D000077265:Donepezil; D012601:Scopolamine