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Volume 17, Number 9, Issue of May 1, 1997 pp. 3168-3177
Copyright ©1997 Society for Neuroscience

PET Measurement of Dopamine D₂ Receptor-Mediated Changes in Striatopallidal Function

Received Jan. 6, 1997; accepted Feb. 11, 1997.

Kevin J. Black^{1, 2}, Mokhtar H. Gado¹, and Joel S. Perlmutter¹

¹ Departments of Radiology, Neurology and Neurological Surgery, and ² Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63130

This study was designed to validate an in vivo measurement of the functional sensitivity of basal ganglia neuronal circuits containing dopamine D₂ receptors. We hypothesized that a D₂ agonist would decrease striatopallidal neuronal activity, and hence regional cerebral blood flow (rCBF) over the axon terminals in the globus pallidus. Quantitative pallidal blood flow was measured using positron emission tomography (PET) with bolus injections of H₂¹⁵O and arterial sampling in six baboons before and after intravenous administration of the selective D₂ agonist U91356a. We also tested whether the response to U91356a was modified by previous acute administration of various antagonists. Another baboon had serial measurements of blood flow under identical conditions, but received no dopaminergic drugs. In all animals that received U91356a, pallidal flow decreased in a dose-related manner. Global CBF had a similar response, but the decline in pallidal flow was greater in magnitude and remained significant after accounting for the global effect. A D₂ antagonist, but not antagonists of D₁, serotonin-2, or peripheral D₂ receptors, prevented this decrease. This work demonstrates and validates an in vivo measure of the sensitivity of D₂-mediated basal ganglia pathways. It also supports the hypothesis that activation of the indirect striatopallidal pathway, previously demonstrated using nonselective D₂-like agonists, can be mediated specifically by D₂ receptors. We speculate that the U91356a-PET technique may prove useful in detecting functional abnormalities of D₂-mediated dopaminergic function in diseases such as parkinsonism, dystonia, Tourette syndrome, or schizophrenia.

Key words: globus pallidus; dopamine D2 receptor; positron emission tomography; pharmacological activation; baboon; U91356a

This article has been cited by other articles:

				K. J. Black, T. Hershey, J. M. Koller, T. O. Videen, M. A. Mintun, J. L. Price, and J. S. Perlmutter A possible substrate for dopamine-related changes in mood and behavior: Prefrontal and limbic effects of a D3-preferring dopamine agonist PNAS, December 24, 2002; 99(26): 17113 - 17118. [Abstract] [Full Text] [PDF]

				M. Hallett Blepharospasm: Recent advances Neurology, November 12, 2002; 59(9): 1306 - 1312. [Abstract] [Full Text] [PDF]

				J. S. Perlmutter, J. W. Mink, A. J. Bastian, K. Zackowski, T. Hershey, E. Miyawaki, W. Koller, and T. O. Videen Blood flow responses to deep brain stimulation of thalamus Neurology, May 14, 2002; 58(9): 1388 - 1394. [Abstract] [Full Text] [PDF]

				K. J. Black, T. Hershey, M. H. Gado, and J. S. Perlmutter Dopamine D1 Agonist Activates Temporal Lobe Structures in Primates J Neurophysiol, July 1, 2000; 84(1): 549 - 557. [Abstract] [Full Text] [PDF]

				T. Hershey, K. J. Black, M. K. Stambuk, J. L. Carl, L. A. McGee-Minnich, and J. S. Perlmutter Altered thalamic response to levodopa in Parkinson's patients with dopa-induced dyskinesias PNAS, September 29, 1998; 95(20): 12016 - 12021. [Abstract] [Full Text] [PDF]

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