Deciphering the scopolamine challenge rat model by preclinical functional MRI

Abstract During preclinical drug testing, the systemic administration of scopolamine (SCO), a cholinergic antagonist, is widely used. However, it suffers important limitations, like non-specific behavioural effects partly due to its peripheral side-effects. Therefore, neuroimaging measures would enh...

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Autores principales: Gergely Somogyi, Dávid Hlatky, Tamás Spisák, Zsófia Spisák, Gabriella Nyitrai, András Czurkó
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/bc375befec4241b7a5e689a909becee5
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spelling oai:doaj.org-article:bc375befec4241b7a5e689a909becee52021-12-02T14:49:10ZDeciphering the scopolamine challenge rat model by preclinical functional MRI10.1038/s41598-021-90273-92045-2322https://doaj.org/article/bc375befec4241b7a5e689a909becee52021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90273-9https://doaj.org/toc/2045-2322Abstract During preclinical drug testing, the systemic administration of scopolamine (SCO), a cholinergic antagonist, is widely used. However, it suffers important limitations, like non-specific behavioural effects partly due to its peripheral side-effects. Therefore, neuroimaging measures would enhance its translational value. To this end, in Wistar rats, we measured whisker-stimulation induced functional MRI activation after SCO, peripherally acting butylscopolamine (BSCO), or saline administration in a cross-over design. Besides the commonly used gradient-echo echo-planar imaging (GE EPI), we also used an arterial spin labeling method in isoflurane anesthesia. With the GE EPI measurement, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In a second experiment, we used GE EPI and spin-echo (SE) EPI sequences in a combined (isoflurane + i.p. dexmedetomidine) anesthesia to account for anesthesia-effects. Here, we also examined the effect of donepezil. In the combined anesthesia, with the GE EPI, SCO decreased the activation in the BC and the inferior colliculus (IC). BSCO reduced the response merely in the IC. Our results revealed that SCO attenuated the evoked BOLD activation in the BC as a probable central effect in both experiments. The likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.Gergely SomogyiDávid HlatkyTamás SpisákZsófia SpisákGabriella NyitraiAndrás CzurkóNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Gergely Somogyi
Dávid Hlatky
Tamás Spisák
Zsófia Spisák
Gabriella Nyitrai
András Czurkó
Deciphering the scopolamine challenge rat model by preclinical functional MRI
description Abstract During preclinical drug testing, the systemic administration of scopolamine (SCO), a cholinergic antagonist, is widely used. However, it suffers important limitations, like non-specific behavioural effects partly due to its peripheral side-effects. Therefore, neuroimaging measures would enhance its translational value. To this end, in Wistar rats, we measured whisker-stimulation induced functional MRI activation after SCO, peripherally acting butylscopolamine (BSCO), or saline administration in a cross-over design. Besides the commonly used gradient-echo echo-planar imaging (GE EPI), we also used an arterial spin labeling method in isoflurane anesthesia. With the GE EPI measurement, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In a second experiment, we used GE EPI and spin-echo (SE) EPI sequences in a combined (isoflurane + i.p. dexmedetomidine) anesthesia to account for anesthesia-effects. Here, we also examined the effect of donepezil. In the combined anesthesia, with the GE EPI, SCO decreased the activation in the BC and the inferior colliculus (IC). BSCO reduced the response merely in the IC. Our results revealed that SCO attenuated the evoked BOLD activation in the BC as a probable central effect in both experiments. The likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.
format article
author Gergely Somogyi
Dávid Hlatky
Tamás Spisák
Zsófia Spisák
Gabriella Nyitrai
András Czurkó
author_facet Gergely Somogyi
Dávid Hlatky
Tamás Spisák
Zsófia Spisák
Gabriella Nyitrai
András Czurkó
author_sort Gergely Somogyi
title Deciphering the scopolamine challenge rat model by preclinical functional MRI
title_short Deciphering the scopolamine challenge rat model by preclinical functional MRI
title_full Deciphering the scopolamine challenge rat model by preclinical functional MRI
title_fullStr Deciphering the scopolamine challenge rat model by preclinical functional MRI
title_full_unstemmed Deciphering the scopolamine challenge rat model by preclinical functional MRI
title_sort deciphering the scopolamine challenge rat model by preclinical functional mri
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/bc375befec4241b7a5e689a909becee5
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