TY - JOUR
T1 - Subcortical dopaminergic deficits in a DISC1 mutant model
T2 - A study in direct reference to human molecular brain imaging
AU - Jaaro-Peled, Hanna
AU - Niwa, Minae
AU - Foss, Catherine A.
AU - Murai, Rina
AU - Reyes, Samantha de los
AU - Kamiya, Atsushi
AU - Mateo, Yolanda
AU - O'Donnell, Patricio
AU - Cascella, Nicola G.
AU - Nabeshima, Toshitaka
AU - Guilarte, Tomás R.
AU - Pomper, Martin G.
AU - Sawa, Akira
PY - 2013/4
Y1 - 2013/4
N2 - Imaging of the human brain has been an invaluable aid in understanding neuropsychopharmacology and, in particular, the role of dopamine in the striatum in mental illness. Here, we report a study in a genetic mouse model for major mental illness guided by results from human brain imaging: a systematic study using small animal positron emission tomography (PET), autoradiography, microdialysis and molecular biology in a putative dominant-negative mutant DISC1 transgenic model. This mouse model showed augmented binding of radioligands to the dopamine D2 receptor (D2R) in the striatum as well as neurochemical and behavioral changes to methamphetamine administration. Previously we reported that this model displayed deficits in the forced swim test, a representative indicator of antidepressant efficacy. By combining the results of our two studies, we propose a working hypothesis for future studies that this model might represent a mixed condition of depression and psychosis. We hope that this study will also help bridge a major gap in translational psychiatry between basic characterization of animal models and clinico-pharmacological assessment of patients mainly through PET imaging.
AB - Imaging of the human brain has been an invaluable aid in understanding neuropsychopharmacology and, in particular, the role of dopamine in the striatum in mental illness. Here, we report a study in a genetic mouse model for major mental illness guided by results from human brain imaging: a systematic study using small animal positron emission tomography (PET), autoradiography, microdialysis and molecular biology in a putative dominant-negative mutant DISC1 transgenic model. This mouse model showed augmented binding of radioligands to the dopamine D2 receptor (D2R) in the striatum as well as neurochemical and behavioral changes to methamphetamine administration. Previously we reported that this model displayed deficits in the forced swim test, a representative indicator of antidepressant efficacy. By combining the results of our two studies, we propose a working hypothesis for future studies that this model might represent a mixed condition of depression and psychosis. We hope that this study will also help bridge a major gap in translational psychiatry between basic characterization of animal models and clinico-pharmacological assessment of patients mainly through PET imaging.
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U2 - 10.1093/hmg/ddt007
DO - 10.1093/hmg/ddt007
M3 - Article
C2 - 23314019
AN - SCOPUS:84875764541
SN - 0964-6906
VL - 22
SP - 1574
EP - 1580
JO - Human molecular genetics
JF - Human molecular genetics
IS - 8
ER -