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.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Mohler EG,Ding Z,Rueter LE,Chapin D,Young D,Kozak Rdoi
10.1007/s00213-015-4012-0subject
Has Abstractpub_date
2015-11-01 00:00:00pages
4033-41issue
21-22eissn
0033-3158issn
1432-2072pii
10.1007/s00213-015-4012-0journal_volume
232pub_type
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更新日期:2014-02-01 00:00:00
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pub_type: 杂志文章,已发布勘误
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更新日期:2018-09-01 00:00:00
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更新日期:1986-01-01 00:00:00
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更新日期:2012-05-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:2000-05-01 00:00:00
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journal_title:Psychopharmacology
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更新日期:2020-11-25 00:00:00
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journal_title:Psychopharmacology
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更新日期:1994-09-01 00:00:00
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更新日期:2005-08-01 00:00:00
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