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Abstract #0913

In Vivo Evaluation of the Specificity of Novel Drugs Targeting Dopamine D3 Receptors Using MRI: Role of Positive and Negative Hemodynamic Indices

Ji-Kyung Choi1, Joseph B. Mandeville1, Y. Iris Chen1, Peter Grundt2, Amy H. Newman3, Bruce G. Jenkins1

1Radiology, Athinoula Martinos Center for Biomedical Imaging, Charlestown, MA, USA; 2Medicinal Chemistry, NIDA, Baltimore, MD; 3Medicinal Chemistry, NIDA, Baltimore, MD, USA

Identifying the specificity of novel drugs targeting brain receptors is difficult and often requires synthesis of a radiolabel to determine in vivo specificity. We demonstrate the utility of pharmacologic MRI for identifying the specificity of dopamine D3 receptor drugs. D3 antagonists induce positive CBV and D3 agonists negative CBV changes in brain regions corresponding to the distribution of D3 receptors. Further, we show that these drugs induce positive CBV changes in cortical laminae with D1 receptors and negative CBV changes in cortical laminae with D3 recpetor innervation. MRI should prove to be a useful tool for characterization of novel drugs.