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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2021
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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) |
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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 |
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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 |
work_keys_str_mv |
AT gergelysomogyi decipheringthescopolaminechallengeratmodelbypreclinicalfunctionalmri AT davidhlatky decipheringthescopolaminechallengeratmodelbypreclinicalfunctionalmri AT tamasspisak decipheringthescopolaminechallengeratmodelbypreclinicalfunctionalmri AT zsofiaspisak decipheringthescopolaminechallengeratmodelbypreclinicalfunctionalmri AT gabriellanyitrai decipheringthescopolaminechallengeratmodelbypreclinicalfunctionalmri AT andrasczurko decipheringthescopolaminechallengeratmodelbypreclinicalfunctionalmri |
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1718389531945730048 |