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Abstract #2097

Positive allosteric modulation of the metabotropic glutamate receptor subtype 5 modulates dopaminergic brain circuits

Nellie Byun 1,2 , Robert L Barry 3 , Richard Baheza 2 , Stephen Damon 4 , John C Gore 2 , and P Jeffrey Conn 1

1 Vanderbilt Center for Neuroscience Drug Discovery, Nashville, TN, United States, 2 Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, 3 Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashviille, TN, United States, 4 Neurology, Vanderbilt University Medical Center, Nashville, TN, United States

We performed functional connectivity and permutation analyses on two pharmacological MRI (phMRI) data sets to identify statistically significant differences between circuit correlations observed in (1) the amphetamine response versus (2) modulation of the amphetamine response by VU0360172 a compound that targets the metabotropic glutamate receptor subtype 5, a target for the treatment of schizophrenia. Correlation analysis of the phMRI responses, a translational approach for characterizing drug-related functional connectivity patterns, provided more information than traditional individual ROI amplitude results, revealing modulation of circuits connected to entorhinal, cingulate, and motor cortices, and striatum.

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