1. Mapping and quantification of dopamine D2 receptor activation
Kevin J. Black, Tamara Hershey, Jonathan M. Koller, Juanita L. Carl, Joel S. Perlmutter
Departments of Psychiatry, Neurology, Radiology, and Anatomy and Neurobiology, Washington University School of Medicine, and
School of Engineering, Washington University

2. Methods 4 normal baboons, 5 study days
ventilated with 70% N2O throughout the study
U91356a (antiparkinsonian dose ~ mg/kg); Ki’s:
D2 = 1.3nM; D3 = 32nM; D4 = 195nM
D1 > 1000nM
5HT1A = 58nM
PET rCBF scans before, after mg/kg iv
PET methods validated in baboons (Herscovitch et al., 1983; Raichle et al., 1983; Videen et al., 1987)
scans aligned to the b2k atlas ( (Black et al 2001)
analysis with SPM99 as previously described (Black et al, 2000)

3. Results 1 relative CBF increases:
A single large (20cc) contiguous cluster of voxels with p < 0.001, peak t > 8 (34 d.f.), corrected p «
Peaks in cerebellum, temporal poles, amygdala, edge of brain
relative CBF decreases:
5 significant clusters
Peak t > 7.5 (34 d.f.), corrected p «
Peaks in dorsolateral prefrontal cortex, putamen, medial parietal and posterior cingulate cortex, primary sensorimotor cortex, and superior temporal gyrus

4. Results 2: rCBF decreases (NOTE: significant values imply decreases disproportionate to any global changes)

5. Results 3: rCBF decreases
Time course of DLPFC peak:
stable response over 1hr T
(mean ± S.D.)

6. Results 4: whole-brain CBF
Average blood flow throughout the brain decreased after U91356a (below left)
Thus the “increases” are really areas spared this effect (see graph below right)
These results can only be interpreted correctly because we used quantitative methods

7. U91356a rCBF changes are pharmacologically specific (ROIs centered on L & R GPi, averaged – from Black et al, 1997)
D2 antag
D1 antag
peripheral D2
S2 antag

8. Conclusions
The D2-specific dopamine agonist U91356a decreases whole-brain blood flow by ~30%
Even after accounting for this global change, there are statistically very robust regional decreases
In approximate descending order of significance these decreases have peak statistical values in:
dorsolateral prefrontal cortex, putamen, medial parietal and posterior cingulate cortex, primary sensorimotor cortex, and superior temporal gyrus

9. Discussion
The pattern of blood flow changes after dopamine agonists depends on the drug’s receptor specificity (see next page)
These results can help inform pharmacologic challenge neuroimaging results in humans with less specific agonists (see next page)
A challenge test such as this one may lend itself to quantifying the brain’s responses to stimulation of receptor-specific neuronal pathways in human disease states

11. Acknowledgments
Funding: NINDS (NS01898 and others), NARSAD Young Investigator Award (K.J.B.), Tourette Syndrome Association, Charles A. Dana Foundation, American Parkinson Disease Association, and McDonnell Center for Higher Brain Function.
U91356a was a gift from Upjohn.
Technical support: Terry Anderson, Craig Collins, John Hood Jr., Bettina Tobben, Lennis Lich