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Abstract
During preclinical drug testing, the systemic administration scopolamine (SCO), a cholinergic antagonist, is widely used. However, it has limited predictive validity partly due to its peripheral side-effects. Therefore, objective 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. 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.
Significance Statement Rodent functional MRI (fMRI) is a powerful and promising tool for translational research, as it bridges the gap between animal experiments and human neuroimaging. Scopolamine (SCO) is a standard reference drug for inducing experimental cognitive impairment in both animals and humans, however, it has limited predictive validity partly due to its peripheral side-effects. We measured whisker-stimulation induced fMRI activation after injecting SCO or its peripherally acting analog with different fMRI sequences in two different anesthesia type and analyzed the data with different statistical inferences. We deciphered that the likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
* Abstract revised, Significance Statement added, Figure 4 revised, Supplementary Material added.