GSBS Student Publications

Title

Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: correlation with PET, microdialysis, and behavioral data

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences

Date

10-27-1997

Document Type

Article

Medical Subject Headings

Adrenergic Agents; Animals; Behavior, Animal; Brain; Cocaine; Dextroamphetamine; Dopamine; Dopamine Uptake Inhibitors; Magnetic Resonance Imaging; Microdialysis; Oxidopamine; Rats; Rats, Sprague-Dawley; Receptors, Dopamine; Sensitivity and Specificity; Tomography, Emission-Computed

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The metabolic activation resulting from direct dopaminergic stimulation 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 ligands: the dopamine release compound D-amphetamine and the dopamine transporter antagonist 2 beta-carbomethoxy-3 beta-(4-fluoropheny) tropane (CFT). Both compounds led to increased signal intensity in gradient echo images in regions of the brain with high dopamine receptor density (frontal cortex, striatum, cingulate cortex > > parietal cortex). Lesioning the animals with unilaterally administered 6-hydroxydopamine (6-OHDA) led to ablation of the phMRI response on the ipsilateral side; control measurements of rCBV and rCBF using bolus injections of Gd-DTPA showed that the baseline rCBV and rCBF values were intact on the lesioned side. The time course of the BOLD signal changes paralleled the changes observed by microdialysis measurements of dopamine release in the striatum for both amphetamine and CFT; peaking at 20-40 min after injection and returning to baseline at about 70-90 min. Signal changes were not correlated with either heart rate, blood pressure or pCO2. Measurement of PET binding in the same animals showed an excellent correlation 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 demonstrate that phMRI will become a valuable, noninvasive tool for investigation of neurotransmitter activity in vivo.

Rights and Permissions

Citation: Magn Reson Med. 1997 Sep;38(3):389-98.

Related Resources

Link to article in PubMed

Journal Title

Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester)

PubMed ID

9339439