Deciphering the scopolamine challenge rat model by preclinical functional MRI.

Area of Science:

• Neuroscience
• Pharmacology
• Medical Imaging

Background:

• Systemic scopolamine (SCO) is used in preclinical drug testing but has limitations due to non-specific behavioral and peripheral effects.
• Neuroimaging can enhance the translational value of scopolamine studies by distinguishing central from peripheral actions.

Purpose of the Study:

• To investigate the central and peripheral effects of scopolamine (SCO) and butylscopolamine (BSCO) on brain activity using functional MRI (fMRI) in Wistar rats.
• To compare the effects of SCO and BSCO under different anesthesia conditions and with different fMRI sequences.

Main Methods:

• Wistar rats underwent whisker-stimulation induced fMRI under various anesthesia regimens (isoflurane, or isoflurane + dexmedetomidine).
• Scopolamine (SCO), butylscopolamine (BSCO), or saline was administered in a cross-over design.
• Gradient-echo echo-planar imaging (GE EPI) and spin-echo (SE) EPI sequences were employed, alongside arterial spin labeling.

Main Results:

• Scopolamine (SCO) decreased evoked BOLD response in the barrel cortex (BC) under both anesthesia conditions, suggesting a central effect.
• Butylscopolamine (BSCO) increased activation in the anterior cingulate cortex with GE EPI under isoflurane anesthesia.
• BSCO reduced activation in the inferior colliculus (IC) under combined anesthesia.
• Peripheral vascular effects of SCO appeared dependent on anesthesia type and dose.

Conclusions:

• Scopolamine (SCO) attenuates evoked BOLD activation in the barrel cortex, likely via central mechanisms.
• The observed fMRI signal changes attributed to peripheral actions of SCO are influenced by anesthesia and fMRI sequence choice.
• Distinguishing central from peripheral drug effects using fMRI requires careful consideration of experimental conditions.