Johnson, Anthony C. and Myers, Brent and Lazovic, Jelena and Towner, Rheal and Greenwood-Van Meerveld, Beverley (2010) Brain Activation in Response to Visceral Stimulation in Rats with Amygdala Implants of Corticosterone: An fMRI Study. PLoS ONE, 5 (1). e8573. ISSN 1932-6203 http://resolver.caltech.edu/CaltechAUTHORS:20100201-115008820
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Background: Although visceral pain of gastrointestinal (GI) origin is the major complaint in patients with irritable bowel syndrome (IBS) it remains poorly understood. Brain imaging studies suggest a defect in brain-gut communication in IBS with a greater activation of central arousal circuits including the amygdala. Previously, we found that stereotaxic implantation of corticosterone (CORT) onto the amygdala in rats induced anxiety and colonic hypersensitivity. In the present study we used functional magnetic resonance imaging (fMRI) to identify specific brain sites activated in a rat model characterized by anxiety and colonic hypersensitivity. Methodology/Principal Findings: Anesthetized male rats received micropellets (30 µg each) of either CORT or cholesterol (CHOL), to serve as a control, implanted stereotaxically on the dorsal margin of each amygdala. Seven days later, rats were anesthetized and placed in the fMRI magnet (7T). A series of isobaric colorectal balloon distensions (CRD - 90s ‘off’, 30s ‘on’, 8 replicates) at two pressures (40 and 60 mmHg) were performed in a standard block-design. Cross correlation statistical analysis was used to determine significant differences between distended and non-distended states in CORT and CHOL-treated animals. Analysis of the imaging data demonstrated greater overall brain activation in response to CRD in rats with CORT implants compared to CHOL controls. Additionally, CORT implants produced significant positive bilateral increases in MRI signal in response to CRD in specific nuclei known as integration sites important in anxiety and pain perception. Conclusions and Significance: These data indicate that chronic exposure of the amygdala to elevated levels of CORT enhances overall brain activation in response to CRD, and identified other specific brain regions activated in response to mechanical distension of the colon. These results demonstrate the feasibility of performing fMRI imaging in a rodent model that supports clinical observations in IBS patients with enhanced amygdala activation and symptomatology of abdominal pain and anxiety.
|Additional Information:||© 2010 Johnson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received September 18, 2009; accepted December 15, 2009; published January 5, 2010. Editor: Fabien Tell, The Research Center of Neurobiology-Neurophysiology of Marseille, France. This research was supported by the Oklahoma Center for Neuroscience at the University of Oklahoma Health Sciences Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr. BGVM is Career Scientist and she would like to acknowledge the support provided to her from the Department of Veterans Affairs. Preliminary analysis of this data was presented at the Neurogastroenterology and Motility 2006 Joint International Meeting (Boston, MA) and the 38th annual Digestive Disease Week, 2007 (Washington D.C.). Author Contributions: Conceived and designed the experiments: BGVM. Performed the experiments: ACJ BM JL. Analyzed the data: ACJ BM JL. Contributed reagents/materials/analysis tools: RT. Wrote the paper: ACJ BM JL BGVM.|
|Official Citation:||Johnson AC, Myers B, Lazovic J, Towner R, Greenwood-Van Meerveld B (2010) Brain Activation in Response to Visceral Stimulation in Rats with Amygdala Implants of Corticosterone: An fMRI Study. PLoS ONE 5(1): e8573. doi:10.1371/journal.pone.0008573|
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|Deposited By:||Jason Perez|
|Deposited On:||04 Feb 2010 17:18|
|Last Modified:||26 Dec 2012 11:44|
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