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J Cereb Blood Flow Metab. 2012 Apr;32(4):676-84. doi: 10.1038/jcbfm.2011.171. Epub 2011 Dec 14.

The utility of (11)C-arachidonate PET to study in vivo dopaminergic neurotransmission in humans.

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  • 1Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. thambisettym@mail.nih.gov

Abstract

We developed a novel method to study dopaminergic neurotransmission using positron emission tomography (PET) with [1-(11)C]arachidonic acid ([1-(11)C]AA). Previous preclinical studies have shown the utility of [1-(11)C]AA as a marker of signal transduction coupled to cytosolic phospholipase A(2) (cPLA(2)). Using [1-(11)C]AA and [(15)O]water PET, we measured regional incorporation coefficients K(*) for AA and regional cerebral blood flow (rCBF), respectively, in healthy male volunteers given the D(1)/D(2) agonist (10 or 20 μg/kg subcutaneous) apomorphine. We confirmed a robust central dopaminergic response to apomorphine by observing significant increases in the serum concentration of growth hormone. We observed significant increases, as well as decreases in K(*) and increases in rCBF in response to apomorphine. These changes remained significant after covarying for handedness and apomorphine dosage. The magnitude of increases in K(*) was lower than those in our previous animal experiments, likely reflecting the smaller dose of apomorphine used in the current human study. Changes in K(*) may reflect neuronal signaling downstream of activated D(2)-like receptors coupled to cPLA(2). Changes in rCBF are consistent with previous studies showing net functional effects of D(1)/D(2) activation. [1-(11)C]AA PET may be useful for studying disturbances of dopaminergic neurotransmission in conditions such as Parkinson's disease and schizophrenia.

PMID:
22167235
[PubMed - indexed for MEDLINE]
PMCID:
PMC3318145
Free PMC Article
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