DETECTION OF DOPAMINERGIC NEUROTRANSMITTER ACTIVITY USING PHARMACOLOGICAL MRI - CORRELATION WITH PET, MICRODIALYSIS, AND BEHAVIORAL-DATA

The metabolic activation resulting from direct dopaminergic stimulatio n can be detected using auto-radiography, positron emission tomography (PET) or, potentially, fMRI techniques. To establish the validity of the latter possibility, we have performed a number of experiments. We measured the regional selectivity of two different dopaminergic ligand s: the dopamine release compound D-amphetamine and the dopamine transp orter antagonist 2 beta-carbomethoxy-3 beta-(4-fluoropheny) tropane (C FT). Both compounds led to increased signal intensity in gradient echo images in regions of the brain with high dopamine receptor density (f rontal cortex, striatum, cingulate cortex >> parietal cortex). Lesioni ng the animals with unilaterally administered 6-hydroxydopamine (6-OHD A) led to ablation of the phMRI response on the ipsilateral side; cont rol measurements of rCBV and rCBF using bolus injections of Gd-DTPA sh owed that the baseline rCBV and rCBF values were intact on the lesione d side. The time course of the BOLD signal changes paralleled the chan ges observed by microdialysis measurements of dopamine release in the striatum for both amphetamine and CFT; peaking at 20-40 min after inje ction and returning to baseline at about 70-90 min. Signal changes wer e not correlated with either heart rate, blood pressure or pCO(2). Mea surement of PET binding in the same animals showed an excellent correl ation with the phMRI data when compared by either measurements of the number of pixels activated or percent signal change in a given region. The time course for the behavioral measurements of rotation in the 6- OHDA lesioned animals correlated with the phMRI. These experiments dem onstrate that phMRI will become a valuable, noninvasive tool for inves tigation of neurotransmitter activity in vivo.