Imaging extra-striatal dopamine D2 receptors in a maternal immune activation rat model

Arata Oh-Nishi; Yuji Nagai; Chie Seki; Tetsuya Suhara; Takafumi Minamimoto; Makoto Higuchi

doi:10.1016/j.bbih.2022.100446

Imaging extra-striatal dopamine D2 receptors in a maternal immune activation rat model

Brain Behav Immun Health. 2022 Mar 11:22:100446. doi: 10.1016/j.bbih.2022.100446. eCollection 2022 Jul.

Authors

Arata Oh-Nishi^{1

2

3}, Yuji Nagai¹, Chie Seki¹, Tetsuya Suhara¹, Takafumi Minamimoto¹, Makoto Higuchi¹

Affiliations

¹ Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan.
² Division of Immune-Neuropsychiatry, Faculty of Medicine, Shimane University, Shimane, 693-8501, Japan.
³ RESVO Inc., Kawasaki, 210-007, Japan.

Abstract

Maternal immune activation (MIA) is a risk factor for schizophrenia in the offspring. MIA in pregnant rodents can be induced by injection of synthetic polyriboinosinic-polyribocytidilic acid (Poly I:C), which causes decreased striatal dopamine D2 receptor (D2R) expression and behavioral dysfunction mediated by the dopaminergic system in the offspring. However, previous studies did not determine whether Poly I:C induced cortical dopamine D2R abnormality in an MIA rat model. In this study, we performed micro-positron emission tomography (micro-PET) in vivo imaging and ex vivo neurochemical analyses of cortical D2Rs in MIA. In the micro-PET analyses, the anterior cingulate cortex (ACC) region in the offspring showed significantly reduced binding potential for [¹¹C]FLB457, a high affinity radio-ligand toward D2Rs. Neurochemical analysis showed reduction of D2Rs and augmentation of dopamine turnover in the ACC of the rat offspring. Thus, MIA induces dopaminergic dysfunction in the ACC of offspring, similar to the neuronal pathology reported in patients with schizophrenia.

Keywords: Anterior cingulate cortex; Dopamine; Dopamine D2 receptors; In vivo imaging; MIA rat model; Maternal immune activation; Poly I:C; Positron emission tomography; Schizophrenia; [11C]FLB457.