Subcortical dopaminergic deficits in a DISC1 mutant model: A study in direct reference to human molecular brain imaging

27Citations
Citations of this article
38Readers
Mendeley users who have this article in their library.
Get full text

Abstract

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.

Cite

CITATION STYLE

APA

Jaaro-Peled, H., Niwa, M., Foss, C. A., Murai, R., Reyes, S. de los, Kamiya, A., … Sawa, A. (2013). Subcortical dopaminergic deficits in a DISC1 mutant model: A study in direct reference to human molecular brain imaging. Human Molecular Genetics, 22(8), 1574–1580. https://doi.org/10.1093/hmg/ddt007

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free