Striatal binding of the PET ligand ¹¹C‐raclopride is altered by drugs that modify synaptic dopamine levels

Bilatera 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. © 1993 Wiley‐Liss, Inc.