QUANTITATIVE DOPAMINE RECEPTOR PHARMACODYNAMICS FROM FMRI

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DESCRIPTION (provided by applicant): This project will empirically test whether quantitative information about drug dose effects on brain function can be extracted from functional Magnetic Resonance Imaging (fMRI). We have developed a method for determining the ED50 - the drug dose required to produce 50 percent of the maximum effect - from data acquired from fMRI blood oxygen level dependent (BOLD) imaging. This method, quantitative pharmacodynamic imaging (QPDI), has been tested with encouraging results on simulated data, and on preliminary data from nonhuman primates. The proposed experiments will test the model with dopamine agonists (SKF82958, pramipexole). Dopamine is a critical neurotransmitter in the brain, and dopaminergic pathways are associated with movement disorders, mental illness and drug abuse. We will measure ED50 for two responses of the brain to the drugs: the effect of dopamine agonists on prolactin secretion will be determined from blood serum samples in the traditional manner (independent measurements for each dose of drug), while changes in brain hemodynamics will be measured in a single experiment using our new QPDI method and fMRI BOLD signal. This method has potentially wide application for testing the brain's response to pharmacological agents for use in scientific research and clinical medicine. PUBLIC HEALTH RELEVANCE: We propose to test a new method for obtaining quantitative pharmacodynamic information from functional magnetic resonance imaging with specific pharmacological agents in a living brain. This method could be used to diagnosis disorders and determine appropriate drug dosage, and could be invaluable for researching physiological mechanisms and developing new drugs for treating diseases.