title: Scopolamine provocation-based pharmacological MRI model for testing procognitive agents.
abstract: There is a huge unmet need to understand and treat pathological cognitive impairment. The development of disease modifying cognitive enhancers is hindered by the lack of correct pathomechanism and suitable animal models. Most animal models to study cognition and pathology do not fulfil either the predictive validity, face validity or construct validity criteria, and also outcome measures greatly differ from those of human trials. Fortunately, some pharmacological agents such as scopolamine evoke similar effects on cognition and cerebral circulation in rodents and humans and functional MRI enables us to compare cognitive agents directly in different species. In this paper we report the validation of a scopolamine based rodent pharmacological MRI provocation model. The effects of deemed procognitive agents (donepezil, vinpocetine, piracetam, alpha 7 selective cholinergic compounds EVP-6124, PNU-120596) were compared on the blood-oxygen-level dependent responses and also linked to rodent cognitive models. These drugs revealed significant effect on scopolamine induced blood-oxygen-level dependent change except for piracetam. In the water labyrinth test only PNU-120596 did not show a significant effect. This provocational model is suitable for testing procognitive compounds. These functional MR imaging experiments can be paralleled with human studies, which may help reduce the number of false cognitive clinical trials.
authors.affiliation: Preclinical Imaging Centre, Gedeon Richter Plc, Budapest, Hungary hegedus.nikolett@gmail.com.
authors.forename: Nikolett
authors.initials: N
authors.lastname: Hegedűs
authors.affiliation: Department of Behavioural Pharmacology, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Laszy
authors.affiliation: Department of Behavioural Pharmacology, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Gyertyán
authors.affiliation: Preclinical Imaging Centre, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Kocsis
authors.affiliation: Preclinical Imaging Centre, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Gajári
authors.affiliation: Preclinical Imaging Centre, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Dávid
authors.affiliation: Preclinical Imaging Centre, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Deli
authors.affiliation: Preclinical Imaging Centre, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Pozsgay
authors.affiliation: Preclinical Imaging Centre, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Tihanyi
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000633:toxicity*; D013045:Species Specificity
chemical_list: D018697:Nootropic Agents; D012601:Scopolamine; D010100:Oxygen
keywords: BOLD; cognition; cognitive enhancer; fMRI; nootropics; rat; scopolamine; water labyrinth test