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Abstract #5316

Etomidate anaesthesia for fMRI in mice revisited: Subcutaneous administration facilitates experimental procedures

Rebecca Klee1, Thomas Mueggler1, Andreas Bruns1, Nicole Wyttenbach1, Antonio Ricci1, Rodolfo Gasser1, Markus von Kienlin1, and Basil K√ľnnecke1

1Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland

Etomidate has recently been proposed as a hypnotic for high-fidelity fMRI in mice. It largely preserves cerebrovascular autoregulation and basal perfusion, thus providing a large window for hemodynamic-based fMRI readouts. However, commercially available formulations of etomidate come at low concentration and are suitable only for intravenous infusion, hence resulting in large infusion volumes and difficult procedures in small rodents. Here, we demonstrate that fMRI-compatible anaesthesia can be readily achieved upon subcutaneous administration of etomidate formulated as aqueous solution. We further propose to substitute etomidate with its short-acting analogue cyclopropyl-methoxycarbonyl metomidate to avert long recovery times due to subcutaneous depot formation.

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