Faculty Collaboration Database

A protocol for use of medetomidine anesthesia in rats for extended studies using task-induced BOLD contrast and resting-state functional connectivity. Neuroimage 2009 Jul 15;46(4):1137-47

Date

03/17/2009

Pubmed ID

19285560

Pubmed Central ID

PMC2693293

DOI

10.1016/j.neuroimage.2009.03.004

Scopus ID

2-s2.0-67349278458 (requires institutional sign-in at Scopus site)   109 Citations

Abstract

The alpha-2-adrenoreceptor agonist, medetomidine, which exhibits dose-dependent sedative effects and is gaining acceptance in small-animal functional magnetic resonance imaging (fMRI), has been studied. Rats were examined on the bench using the classic tail-pinch method with three infusion sequences: 100 microg/kg/h, 300 microg/kg/h, or 100 microg/kg/h followed by 300 microg/kg/h. Stepping the infusion rate from 100 to 300 microg/kg/h after 2.5 h resulted in a prolonged period of approximately level sedation that cannot be achieved by a constant infusion of either 100 or 300 microg/kg/h. By stepping the infusion dosage, experiments as long as 6 h are possible. Functional MRI experiments were carried out on rats using a frequency dependent electrical stimulation protocol-namely, forepaw stimulation at 3, 5, 7, and 10 Hz. Each rat was studied for a four-hour period, divided into two equal portions. During the first portion, rats were started at a 100 microg/kg/h constant infusion. During the second portion, four secondary levels of infusion were used: 100, 150, 200, and 300 microg/kg/h. The fMRI response to stimulation frequency was used as an indirect measure of modulation of neuronal activity through pharmacological manipulation. The frequency response to stimulus was attenuated at the lower secondary infusion dosages 100 or 150 microg/kg/h but not at the higher secondary infusion dosages 200 or 300 microg/kg/h. Parallel experiments with the animal at rest were carried out using both electroencephalogram (EEG) and functional connectivity MRI (fcMRI) methods with consistent results. In the secondary infusion period using 300 microg/kg/h, resting-state functional connectivity is enhanced.

Author List

Pawela CP, Biswal BB, Hudetz AG, Schulte ML, Li R, Jones SR, Cho YR, Matloub HS, Hyde JS

Authors

Hani S. Matloub MD Professor in the Plastic Surgery department at Medical College of Wisconsin
Christopher Pawela PhD Associate Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anesthesia
Animals
Brain
Brain Mapping
Electric Stimulation
Electroencephalography
Hypnotics and Sedatives
Magnetic Resonance Imaging
Male
Medetomidine
Neural Pathways
Rats
Rats, Sprague-Dawley
Rest