Abstract
Medetomidine has become a popular choice for anesthetizing rats during long-lasting sessions of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). Despite this, it has not yet been thoroughly established how commonly reported fMRI readouts evolve over several hours of medetomidine anesthesia and how they are affected by the precise timing, dose, and route of administration. We used four different protocols of medetomidine administration to anesthetize rats for up to six hours and repeatedly evaluated somatosensory stimulus-evoked BOLD responses and resting state functional connectivity. We found that the temporal evolution of fMRI readouts strongly depended on the method of administration. Intravenous administration of a medetomidine bolus (0.05 mg/kg), combined with a subsequent continuous infusion (0.1 mg/kg/h), led to temporally stable measures of stimulus-evoked activity and functional connectivity throughout the anesthesia. Deviating from the above protocol—by omitting the bolus, lowering the medetomidine dose, or using the subcutaneous route—compromised the stability of these measures in the initial two-hour period. We conclude that both an appropriate protocol of medetomidine administration and a suitable timing of fMRI experiments are crucial for obtaining consistent results. These factors should be considered for the design and interpretation of future rat fMRI studies.
Highlights
Medetomidine has become a popular choice for anesthetizing rats during long-lasting sessions of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging
Ethical and practical considerations mandate the use of anesthesia in the majority of small animal functional magnetic resonance imaging (fMRI) studies
A protocol based on the continuous infusion of medetomidine, first introduced by Weber et al.[22], presents several advantages for fMRI studies: it sedates rats for several hours, leads to robust stimulus-evoked BOLD responses, allows for easy subcutaneous (SC) administration, avoids the need for intubation, and can be used for longitudinal studies with multiple fMRI sessions[23]
Summary
Medetomidine has become a popular choice for anesthetizing rats during long-lasting sessions of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). It has not yet been thoroughly established how commonly reported fMRI readouts evolve over several hours of medetomidine anesthesia and how they are affected by the precise timing, dose, and route of administration. A protocol based on the continuous infusion of medetomidine, first introduced by Weber et al.[22], presents several advantages for fMRI studies: it sedates rats for several hours, leads to robust stimulus-evoked BOLD responses, allows for easy subcutaneous (SC) administration, avoids the need for intubation, and can be used for longitudinal studies with multiple fMRI sessions[23]. Its use is expected to rise, owing to the practical advantages and to the increasing availability of techniques that can be combined with rat fMRI
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