Yci. Chen et al., DETECTION OF DOPAMINERGIC NEUROTRANSMITTER ACTIVITY USING PHARMACOLOGICAL MRI - CORRELATION WITH PET, MICRODIALYSIS, AND BEHAVIORAL-DATA, Magnetic resonance in medicine, 38(3), 1997, pp. 389-398
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.