Effects of central cholinergic blockade on striatal dopamine release measured with positron emission tomography in normal human subjects

Stephen L. Dewey, Gwenn S. Smith, Jean Logan, Jonathan D. Brodie, Philip Simkowitz, Robert R. Macgregor, Joanna S. Fowler, Nora D. Volkow, Alfred P. Wolf

Research output: Contribution to journalArticlepeer-review

Abstract

Previously we demonstrated that positron emission tomography (PET) can be used to measure changes in the concentrations of synaptic dopamine and acetylcholine. Whether induced directly or indirectly through interactions with other neurotransmitters, these studies support the use of PET for investigating the functional responsiveness of a specific neurotransmitter to a pharmacologic challenge. In an extension of these findings to the human brain, PET studies designed to measure the responsiveness of striatal dopamine release to central cholinergic blockade were conducted in normal male volunteers using high-resolution PET and [11C]raclopride, a D2-dopamine receptor antagonist. [11C]Raclopride scans were performed prior to and 30 min after systemic administration of the potent muscarinic cholinergic antagonist, scopolamine (0.007 mg/kg). After scopolamine administration, [11C]raclopride binding decreased in the striatum (specific binding) but not in the cerebellum (nonspecific binding) resulting in a significant decrease, exceeding the test/retest variability of this ligand (5%), in the ratio of the distribution volumes of the striatum to the cerebellum (17%). Furthermore, scopolamine administration did not alter the systemic rate of [11C]raclopride metabolism or the metabolite-corrected plasma input function. These results are consistent not only with the known inhibitory influence that acetylcholine exerts on striatal dopamine release but also with our initial 18F-labeled N-methylspiroperidol and benztropine studies. Thus these data support the use of PET for measuring the functional responsiveness of an endogenous neurotransmitter to an indirect pharmacologic challenge in the living human brain.

Original languageEnglish (US)
Pages (from-to)11816-11820
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number24
DOIs
StatePublished - Dec 15 1993
Externally publishedYes

ASJC Scopus subject areas

  • General

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