Journal Article

Acute Morphine Exposure Increases the Brain Distribution of [<sup>18</sup>F]DPA-714, a PET Biomarker of Glial Activation in Nonhuman Primates

Sylvain Auvity, Wadad Saba, Sébastien Goutal, Claire Leroy, Irène Buvat, Jérôme Cayla, Fabien Caillé, Michel Bottlaender, Salvatore Cisternino and Nicolas Tournier

in International Journal of Neuropsychopharmacology

Published on behalf of International College of Neuropsychopharmacology

Volume 20, issue 1, pages 67-71
ISSN: 1461-1457
Published online August 2016 | e-ISSN: 1469-5111 | DOI: http://dx.doi.org/10.1093/ijnp/pyw077
Acute Morphine Exposure Increases the Brain Distribution of [18F]DPA-714, a PET Biomarker of Glial Activation in Nonhuman Primates

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  • Clinical Pharmacology and Therapeutics
  • Neurology
  • Psychiatry
  • Neuroscience

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Abstract

Background:

The neuroinflammatory response to morphine exposure modulates its antinociceptive effects, tolerance, and dependence. Positron emission tomography radioligands for translocator protein-18kDa such as [18F]DPA-714 are noninvasive biomarkers of glial activation, a hallmark of neuroinflammation.

Methods:

[18F]DPA-714 positron emission tomography imaging was performed in 5 baboons at baseline and 2 hours after i.m. morphine injection (1 mg/kg). Brain kinetics and metabolite-corrected input function were measured to estimate [18F]DPA-714 brain distribution.

Results:

Morphine significantly increased [18F]DPA-714 brain distribution by a 1.3 factor (P<.05; paired t test). The effect was not restricted to opioid receptor-rich regions. Differences in baseline [18F]DPA-714 binding were observed among baboons. The response to morphine predominated in animals with the highest baseline uptake.

Conclusions:

[18F]DPA-714 positron emission tomography imaging may be useful to noninvasively investigate the brain immune component of morphine pharmacology. Correlation between baseline brain distribution and subsequent response to morphine exposure suggest a role for priming parameters in controlling the neuroinflammatory properties of opioids.

Keywords: neuroinflammation; TSPO; translocator protein 18 kDa; neuroimmunopharmacology; opioid.

Journal Article.  3121 words.  Illustrated.

Subjects: Clinical Pharmacology and Therapeutics ; Neurology ; Psychiatry ; Neuroscience

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