GABAergic inhibition of endogenous dopamine release measured in vivo with 11C-raclopride and positron emission tomography

S. L. Dewey, G. S. Smith, J. Logan, J. D. Brodie, Wei Yu Ding Wei Yu, R. A. Ferrieri, P. T. King, R. R. MacGregor, T. P. Martin, A. P. Wolf, N. D. Volkow, J. S. Fowler, E. Meller

Research output: Contribution to journalArticlepeer-review

Abstract

Extensive neuroanatomical, neurophysiological, and behavioral evidence demonstrates that GABAergic neurons inhibit endogenous dopamine release in the mammalian corpus striatum. Positron emission tomography (PET) studies in adult female baboons, using the dopamine D2-specific radiotracer 11C- raclopride, were undertaken to assess the utility of this imaging technique for measuring these dynamic interactions in vivo. 11C-raclopride binding was imaged prior to and following the administration of either γ-vinyl-GABA (GVG), a specific suicide inhibitor of the GABA-catabolizing enzyme GABA transaminase, or lorazepam, a clinically prescribed benzodiazepine agonist. Striatal 11C-raclopride binding increased following both GVG and lorazepam administration. This increase exceeded the test/retest variability of 11C- raclopride binding observed in the same animals. These findings confirm that changes in endogenous dopamine concentrations resulting from drug-induced potentiation of GABAergic transmission can be measured with PET and 11C- raclopride. Finally, this new strategy for noninvasively evaluating the functional integrity of neurophysiologically linked transmitter systems with PET supports its use as an approach for assessing the multiple mechanisms of drug action and their consequences in the human brain.

Original languageEnglish (US)
Pages (from-to)3773-3780
Number of pages8
JournalJournal of Neuroscience
Volume12
Issue number10
DOIs
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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