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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