PT  - JOURNAL ARTICLE
AU  - Jongho Kim
AU  - Andrew Horti
AU  - William Mathews
AU  - Heather Valentine
AU  - Hayden Ravert
AU  - Luwei Zhou
AU  - Bruno Jedynak
AU  - Vladimir Pogorelov
AU  - Mikhail Pletnikov
AU  - Dean Wong
TI  - Quantitative in vitro multimodal brain autoradiography of glutamatergic, dopaminergic, cannabinoid, and nicotinic receptors in Disrupted-In-Schizophrenia-1 (DISC1) mice
DP  - 2011 May 01
TA  - Journal of Nuclear Medicine
PG  - 1178--1178
VI  - 52
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/52/supplement_1/1178.short
4100  - http://jnm.snmjournals.org/content/52/supplement_1/1178.full
SO  - J Nucl Med2011 May 01; 52
AB  - 1178 Objectives The aim is to quantify distribution of glutamatergic [metabotropic glutamate 5 (mGluR5)]; dopaminergic [dopamine 2 /3 (D2/3R)]; cannabinoid-1 (CB1R); and nicotinic acetylcholine (nAchR) receptors in DISC1 mice. Methods In vitro quantitative autoradiography using phosphor imaging was performed in control (CTRL) (n=4) and mutant DISC1 (n=4) male mice with 3 sagittal slices (20 µm) of 2, 1.5 and 1 mm to left from midline using 11C-raclopride (D2/3R), 11C-ABP688 (mGluR5), 18F-AZAN (nAChR) and 11C-OMAR (CB1R). Digital light unit was measured using ImageJ (NIH) and coregistration algorithm with histology. Total binding (TB) (pmol/cc) fit from standard and Binding index (BI) defined as [(ROI-reference)/reference] were analyzed. Results In contrast to CTRL, BI in DISC1 showed a significant increase in frontal mGluR5, decrease in striatal D2/3R, increase in hippocampal CB1R, and decrease in dorsal thalamic nACh (p<0.05; Wilcoxon signed rank, 12 by 12 slices, respectively). Correlation studies using TB showed positive correlations of mGluR5 between frontal cortex and hippocampus in both groups(rho=-0.99, p=0.01; 4 by 4 mice, respectively). Frontal and hippocampal mGluR5 was inversely proportional to striatal D2/3R in CTRL (rho=-0.95; p=0.05, respectively), but not in DISC1. Striatal D2/3R showed trends of inverse relationship with striatal CB1R in CTRL, with dorsal thalamic nAchR in DISC1, respectively. Conclusions The mild down-regulation of striatal D2/3R may be related to dominant-negative effects of mutant DISC1 on endogenous DISC1, impacting DR downstream signaling pathways. Multiple neuroreceptor mapping and interactions in DISC1 might be useful for psychiatric drug develoment. Research Support NIBIB, NIDA, NIAAA (5T32EB006351-05) (JK),NIDA 5R33DA016182-05 (W.B.M), ARRA RO1NIMH and NARSAD (MVP