title: Acute Morphine Exposure Increases the Brain Distribution of [18F]DPA-714, a PET Biomarker of Glial Activation in Nonhuman Primates.
abstract: 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.
  
  
  
  [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.
  
  
  
  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.
  
  
  
  [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.
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Sylvain
authors: S
authors: Auvity
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Wadad
authors: W
authors: Saba
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Sébastien
authors: S
authors: Goutal
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Claire
authors: C
authors: Leroy
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Irène
authors: I
authors: Buvat
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Jérôme
authors: J
authors: Cayla
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Fabien
authors: F
authors: Caillé
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Michel
authors: M
authors: Bottlaender
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Salvatore
authors: S
authors: Cisternino
authors: Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, Inserm, Université Paris Descartes, Faculté de pharmacie, Université Paris Diderot, UMR-S 1144, Paris,France.
authors: Nicolas
authors: N
authors: Tournier
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000276:immunology; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects* / Q000276:immunology; D048530:Papio anubis; D010306:Parotid Gland / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
chemical_list: D005462:Fluorine Radioisotopes; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D009294:Narcotics; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D009020:Morphine; C000615276:Fluorine-18
keywords: TSPO; neuroimmunopharmacology; neuroinflammation; opioid; translocator protein 18 kDa