Striatal binding of the PET ligand 11C-raclopride is altered by drugs that modify synaptic dopamine levels.
Bilateral decreases in striatal 11C-raclopride binding were observed in adult female baboons with high resolution PET following administration of drugs that act centrally on dopaminergic neurons. At baseline and following administration of d-amphetamine (a dopamine-releasing drug), GBR-12909 (a potent dopamine reuptake inhibitor), or tetrabenazine (a biogenic amine depleting drug) PET scans of 11C-raclopride binding were obtained in a CTI 931 positron tomograph. In all studies, the ratio of the distribution volumes for the striatum to the cerebellum for 11C-raclopride binding decreased significantly by an average of 16.2% for d-amphetamine, 22.1% for GBR-12909, and 28.3% for tetrabenazine while there were no significant changes observed in the cerebellum or in the rate of systemic metabolism of the radiotracer. These decreases exceed the test/retest variability of striatal 11C-raclopride binding measured in the same animals under identical experimental conditions (Dewey et al., 1992b). Together these studies demonstrate that PET measurements of striatal 11C-raclopride binding can be used to indirectly and non-invasively monitor changes in synaptic dopamine concentrations that result from a variety of neurophysiologic mechanisms.
Dewey
S L
SL
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973.
Smith
G S
GS
Logan
J
J
Brodie
J D
JD
Fowler
J S
JS
Wolf
A P
AP
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D010215:Papio; D010879:Piperazines / Q000494:pharmacology; D020891:Raclopride; D012457:Salicylamides / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013747:Tetrabenazine / Q000494:pharmacology; D014055:Tomography, Emission-Computed
D065127:Dopamine D2 Receptor Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D012457:Salicylamides; D020891:Raclopride; C043425:vanoxerine; D003913:Dextroamphetamine; D004298:Dopamine; D013747:Tetrabenazine