RT Journal Article SR Electronic T1 Quantitative in vitro multimodal brain autoradiography of glutamatergic, dopaminergic, cannabinoid, and nicotinic receptors in Disrupted-In-Schizophrenia-1 (DISC1) mice JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1178 OP 1178 VO 52 IS supplement 1 A1 Jongho Kim A1 Andrew Horti A1 William Mathews A1 Heather Valentine A1 Hayden Ravert A1 Luwei Zhou A1 Bruno Jedynak A1 Vladimir Pogorelov A1 Mikhail Pletnikov A1 Dean Wong YR 2011 UL http://jnm.snmjournals.org/content/52/supplement_1/1178.abstract 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