title: Cross-site strain comparison of pharmacological deficits in the touchscreen visual discrimination test.
abstract: The low rate of success for identifying effective treatments for cognitive dysfunction has prompted recent efforts to improve pharmaceutical discovery and development. In particular, investigators have emphasized improving translation from pre-clinical to clinical research. A specific area of focus has been touchscreen technology; this computer-automated behavioral testing method provides an objective assessment of performance that can be used across species. As part of a larger multi-site study with partners from the Innovative Medicines Initiative (IMI), two US sites, AbbVie and Pfizer, conducted a cross-site experiment with a common protocol for the visual discrimination (VD) task using identical testing equipment, stimuli, and rats of the same strains, sex, and age from the same supplier. As most touchscreen-based rodent experiments have used Lister-Hooded rats that are not readily available outside of Europe, a strain comparison with male Long-Evans rats was conducted as part of the study. Rats were trained for asymptotic performance, and test sessions were performed once per week in a full crossover design with cognition-impairing drugs. Drugs tested were phencyclidine and S-ketamine (N-methyl-D-aspartate (NMDA) antagonists), D-amphetamine (indirect dopamine agonist), and scopolamine (muscarinic antagonist). Satellite brain and plasma samples were taken to confirm appropriate exposures. Results indicate that both rat strains show similar patterns of impairment, although Lister-Hooded rats were more sensitive than Long-Evans rats to three out of four drugs tested. This suggests that researchers should fully explore dose-response relationships in their strain of choice and use care in the interpretation of reversal of cognitive impairment.
authors.affiliation: Neuroscience Discovery Research, AbbVie, North Chicago, IL, 60064, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Mohler
authors.affiliation: Neuroscience Discovery Research, AbbVie, North Chicago, IL, 60064, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Neuroscience Discovery Research, AbbVie, North Chicago, IL, 60064, USA.
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Rueter
authors.affiliation: CNS Biology, Pfizer Inc., 610 Main St., Cambridge, MA, 02142, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Chapin
authors.affiliation: CNS Biology, Pfizer Inc., 610 Main St., Cambridge, MA, 02142, USA.
authors.forename: Damon
authors.initials: D
authors.lastname: Young
authors.affiliation: CNS Biology, Pfizer Inc., 610 Main St., Cambridge, MA, 02142, USA. Rouba.Kozak@Pfizer.com.
authors.forename: Rouba
authors.initials: R
authors.lastname: Kozak
mesh_terms: D000818:Animals; D002755:Choice Behavior / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology; D005060:Europe; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012601:Scopolamine / Q000494:pharmacology*; D014796:Visual Perception / Q000187:drug effects*
chemical_list: D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D007649:Ketamine; D012601:Scopolamine; D010622:Phencyclidine; D003913:Dextroamphetamine
keywords: Amphetamine; Dopamine agonist; Ketamine; Muscarinic antagonist; NMDA antagonist; Phencyclidine; Scopolamine; Touchscreen; Visual discrimination