Visualizing the effects of scopolamine in the rat brain using functional MRI

Cash, Diana; Roberts, Toby J; Ireland, M D; Williams, Steve; Hunter, Jacqueline A; Upton, Neil; Virley, David

doi:10.1038/sj.jcbfm.9591524.0366

Cited by 3 publications

(4 citation statements)

References 2 publications

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“…That study concluded that the effects of scopolamine are probably mainly due to vascular responses. Another study, however, showed that butyl-scopolamine did not induce brain activation changes measured with fMRI (Cash et al, 2005). Differences between these studies include anesthesia protocols i.e.…”

Section: Discussionmentioning

confidence: 92%

Acute modulation of the cholinergic system in the mouse brain detected by pharmacological resting-state functional MRI

et al. 2015

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Section: Discussionmentioning

confidence: 92%

Acute modulation of the cholinergic system in the mouse brain detected by pharmacological resting-state functional MRI

et al. 2015

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“…One of the limitations of the SCO model is its peripheral side-effects that can influence the learning and memory deficits at higher doses of SCO 4 . In a preclinical pharmaco-MRI study the 1 mg/kg SCO and BSCO performed similarly in isoflurane anesthesia 14 , while in α-chloralose anesthesia the 0.8 mg/kg SCO increased the BOLD contrast in the frontal cortex but the same dose of BSCO, not 15 . Importantly, in an eminent translational study of the SCO model, 0.3 mg/kg dose of SCO was used, in rats 6 .…”

Section: Discussionmentioning

confidence: 95%

“…However, in α-chloralose anesthesia in a similar preclinical pharmaco-MRI study, increased BOLD contrast in the frontal (orbital) cortex and olfactory nuclei were found after the i.v. injection of SCO while it was absent after BSCO 15 . These diverging results highlight the difficulty of interpreting preclinical pharmaco-MRI data 16 complicated by the use of different anesthetic regimes 17 , 18 that can introduce potential confounds 19 .…”

Section: Introductionmentioning

confidence: 91%

Deciphering the scopolamine challenge rat model by preclinical functional MRI

Somogyi¹,

Hlatky²,

Spisák³

et al. 2021

Sci Rep

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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.

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“…However, in α-chloralose anesthesia in a similar preclinical pharmaco-MRI study, the SCO i.v. injection increased the BOLD contrast in the frontal (orbital) cortex and olfactory nuclei while it was absent after BSCO injection [11]. These diverging results highlight the difficulty interpreting preclinical pharmaco-MRI data [12] complicated by the use of different anesthetic regimes [13] that can introduce potential confounds [14].…”

Section: Introductionmentioning

confidence: 99%

Deciphering the scopolamine challenge rat model by preclinical functional MRI

Somogyi

Hlatky

Spisák³

et al. 2020

Preprint

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Systemic administration of cholinergic antagonist scopolamine (SCO) is a widely used model to induce experimental cognitive impairment during preclinical drug testing of putative procognitive compounds. This model, however, has limited predictive validity partly due to its peripheral side-effects, therefore objective neuroimaging measures would greatly enhance its translational value. To this end, we administered SCO and peripherally acting butylscopolamine (BSCO) in preclinical functional MRI (fMRI, 9.4T) studies and measured their effects on whisker stimulation induced fMRI activation in Wistar rats. Beside the commonly used gradient echo echo-planar imaging (GE EPI) an arterial spin labeling method was also used to elucidate the vasculature-related properties of the BOLD-response. To account for anesthesia-effects, in two separate experiments we used isoflurane and combined (isoflurane + i.p. dexmedetomidine) anesthesia. In the second experiment with GE EPI and spin echo (SE) EPI sequences the effect of donepezil (DON) was also examined. In isoflurane anesthesia with GE EPI, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In the combined anesthesia SCO decreased the activation in the BC as well as in the inferior colliculus (IC) while 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 while its other detected actions depended on the type of anesthesia or dose and the given fMRI sequences.

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Visualizing the effects of scopolamine in the rat brain using functional MRI

Cited by 3 publications

References 2 publications

Acute modulation of the cholinergic system in the mouse brain detected by pharmacological resting-state functional MRI

Acute modulation of the cholinergic system in the mouse brain detected by pharmacological resting-state functional MRI

Deciphering the scopolamine challenge rat model by preclinical functional MRI

Deciphering the scopolamine challenge rat model by preclinical functional MRI

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